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Connective tissue growth factor is induced in bleomycin-induced skin scleroderma.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
In this report, we use an antibody recognizing CCN2 to assess the cell types in mouse dermis which express CCN2 in the bleomycin model of skin scleroderma. Control (PBS injected) and fibrotic (bleomycin-injected) dermis was examined for CCN2, alpha-smooth muscle actin (alpha-SMA) (to detect myofibroblasts), and NG2 (to detect pericytes) expression. Consistent with previously published data, CCN2 expression was largely absent in the dermis of control mice. However, upon exposure to bleomycin, CCN2 was observed in the dermis. Cells that expressed CCN2 were alpha-SMA-expressing myofibroblasts. Approximately 85% of myofibrobla...
Source: Journal of Cell Communication and Signaling - November 15, 2009 Category: Molecular Biology Authors: Liu S, Taghavi R, Leask A Tags: J Cell Commun Signal Source Type: journals

The role of astrocyte-secreted matricellular proteins in central nervous system development and function.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Matricellular proteins, such as thrombospondins (TSPs1-4), SPARC, SPARC-like1 (hevin) and tenascin C are expressed by astrocytes in the central nervous system (CNS) of rodents. The spatial and temporal expression patterns of these proteins suggest that they may be involved in important developmental processes such as cell proliferation and maturation, cell migration, axonal guidance and synapse formation. In addition, upon injury to the nervous system the expression of these proteins is upregulated, suggesting that they play a role in tissue remodeling and repair in the adult CNS. The genes encoding these proteins have...
Source: Journal of Cell Communication and Signaling - November 11, 2009 Category: Molecular Biology Authors: Eroglu C Tags: J Cell Commun Signal Source Type: journals

Deadly liaisons: fatal attraction between CCN matricellular proteins and the tumor necrosis factor family of cytokines.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Recent studies have revealed an unexpected synergism between two seemingly unrelated protein families: CCN matricellular proteins and the tumor necrosis factor (TNF) family of cytokines. CCN proteins are dynamically expressed at sites of injury repair and inflammation, where TNF cytokines are also expressed. Although TNFalpha is an apoptotic inducer in some cancer cells, it activates NFkappaB to promote survival and proliferation in normal cells, and its cytotoxicity requires inhibition of de novo protein synthesis or NFkappaB signaling. The presence of CCN1, CCN2, or CCN3 overrides this requirement and unmasks the apo...
Source: Journal of Cell Communication and Signaling - November 7, 2009 Category: Molecular Biology Authors: Chen CC, Lau LF Tags: J Cell Commun Signal Source Type: journals

Thrombospondin-2 and SPARC/osteonectin are critical regulators of bone remodeling.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Thrombospondin-2 (TSP2) and osteonectin/BM-40/SPARC are matricellular proteins that are highly expressed by bone cells. Mice deficient in either of these proteins show phenotypic alterations in the skeleton, and these phenotypes are most pronounced under conditions of altered bone remodeling. For example, TSP2-null mice have higher cortical bone volume and are resistant to bone loss associated with ovariectomy, whereas SPARC-null mice have decreased trabecular bone volume and fail to demonstrate an increase in bone mineral density in response to a bone-anabolic parathyroid hormone treatment regimen. In vitro, marrow st...
Source: Journal of Cell Communication and Signaling - October 28, 2009 Category: Molecular Biology Authors: Delany AM, Hankenson KD Tags: J Cell Commun Signal Source Type: journals

Endothelin-1 as a neuropeptide: neurotransmitter or neurovascular effects?email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Endothelin-1 (ET-1) is an endothelium-derived peptide that also possesses potent mitogenic activity. There is also a suggestion the ET-1 is a neuropeptide, based mainly on its histological identification in both the central and peripheral nervous system in a number of species, including man. A neuropeptide role for ET-1 is supported by studies showing a variety of effects caused following its administration into different regions of the brain and by application to peripheral nerves. In addition there are studies proposing that ET-1 is implicated in a number of neural circuits where its transmitter affects range from a ...
Source: Journal of Cell Communication and Signaling - October 21, 2009 Category: Molecular Biology Authors: Dashwood MR, Loesch A Tags: J Cell Commun Signal Source Type: journals

The role of thrombospondins in wound healing, ischemia, and the foreign body reaction.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Thrombospondin (TSP) 1 and TSP2 have been implicated in the regulation of several processes during tissue repair. Due to their matricellular nature, these proteins are thought to modulate cell-matrix interactions through a variety of mechanisms specific to the spatio-temporal context of their expression. Most notably, TSP1 and TSP2 appear to play distinct, non-overlapping roles in the healing of skin wounds. In contrast, both proteins have been implicated as regulators of ischemia-induced angiogenesis. Moreover, TSP2 has been shown to be a critical regulator of angiogenesis in the foreign body response (FBR). In this r...
Source: Journal of Cell Communication and Signaling - October 20, 2009 Category: Molecular Biology Authors: Kyriakides TR, Maclauchlan S Tags: J Cell Commun Signal Source Type: journals

The role of tenascin-C in tissue injury and tumorigenesis.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
The extracellular matrix molecule tenascin-C is highly expressed during embryonic development, tissue repair and in pathological situations such as chronic inflammation and cancer. Tenascin-C interacts with several other extracellular matrix molecules and cell-surface receptors, thus affecting tissue architecture, tissue resilience and cell responses. Tenascin-C modulates cell migration, proliferation and cellular signaling through induction of pro-inflammatory cytokines and oncogenic signaling molecules amongst other mechanisms. Given the causal role of inflammation in cancer progression, common mechanisms might be co...
Source: Journal of Cell Communication and Signaling - October 16, 2009 Category: Molecular Biology Authors: Midwood KS, Orend G Tags: J Cell Commun Signal Source Type: journals

The interaction of Thrombospondins with extracellular matrix proteins.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
The thrombospondins (TSPs) are a family of five matricellular proteins that appear to function as adapter molecules to guide extracellular matrix synthesis and tissue remodeling in a variety of normal and disease settings. Various TSPs have been shown to bind to fibronectin, laminin, matrilins, collagens and other extracellular matrix (ECM) proteins. The importance of TSP-1 in this context is underscored by the fact that it is rapidly deposited at the sites of tissue damage by platelets. An association of TSPs with collagens has been known for over 25 years. The observation that the disruption of the TSP-2 gene in mice...
Source: Journal of Cell Communication and Signaling - October 15, 2009 Category: Molecular Biology Authors: Tan K, Lawler J Tags: J Cell Commun Signal Source Type: journals

A sticky situation: CCN1 promotes both proliferation and apoptosis of cancer cells.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Members of the CCN family of matricellular signaling regulators promote cell adhesion through integrins and heparan sulfate-containing proteoglycans. A paradox of the CCN field is that, depending on the set of circumstances examined, individual CCN molecules can have quite different, and often opposing, effects. In a recent report, Franzen and colleagues (Mol Cancer Res. 7:1045-1055, 2009) show using siRNA knockdown that CCN1 (cyr61) is essential for the proliferation of prostate cancer cells. Intriguingly, on the other hand, CCN1 also enhances TRAIL-induced apoptosis. Thus the utility of anti-CCN1 therapy in cancer ne...
Source: Journal of Cell Communication and Signaling - October 15, 2009 Category: Molecular Biology Authors: Leask A Tags: J Cell Commun Signal Source Type: journals

SPARC: a matricellular regulator of tumorigenesis.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Although many clinical studies have found a correlation of SPARC expression with malignant progression and patient survival, the mechanisms for SPARC function in tumorigenesis and metastasis remain elusive. The activity of SPARC is context- and cell-type-dependent, which is highlighted by the fact that SPARC has shown seemingly contradictory effects on tumor progression in both clinical correlative studies and in animal models. The capacity of SPARC to dictate tumorigenic phenotype has been attributed to its effects on the bioavailability and signaling of integrins and growth factors/chemokines. These molecular pathway...
Source: Journal of Cell Communication and Signaling - October 6, 2009 Category: Molecular Biology Authors: Arnold SA, Brekken RA Tags: J Cell Commun Signal Source Type: journals

The matricellular functions of small leucine-rich proteoglycans (SLRPs).email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
The small leucine-rich proteoglycans (SLRPs) are biologically active components of the extracellular matrix (ECM), consisting of a protein core with leucine rich-repeat (LRR) motifs covalently linked to glycosaminoglycan (GAG) side chains. The diversity in composition resulting from the various combinations of protein cores substituted with one or more GAG chains along with their pericellular localization enables SLRPs to interact with a host of different cell surface receptors, cytokines, growth factors, and other ECM components, leading to modulation of cellular functions. SLRPs are capable of binding to: (i) differe...
Source: Journal of Cell Communication and Signaling - October 1, 2009 Category: Molecular Biology Authors: Merline R, Schaefer RM, Schaefer L Tags: J Cell Commun Signal Source Type: journals

Connective tissue growth factor (CCN2, CTGF) and organ fibrosis: lessons from transgenic animals.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
In recent months, four different systems have been reported in the literature in which CCN2 transgenes were individually expressed in podocytes, hepatocytes, cardiomyocytes or respiratory epithelial cells to achieve overexpression in, respectively, the kidney, liver, heart, or lung. These transgenic systems have provided valuable information about the contribution of CCN2 to fibrosis in vivo and have begun to reveal the complexities of the underlying mechanisms involved. On the one hand, studies of these animals have revealed that CCN2 overexpression does not necessarily lead directly to fibrotic pathology but may caus...
Source: Journal of Cell Communication and Signaling - October 1, 2009 Category: Molecular Biology Authors: Brigstock DR Tags: J Cell Commun Signal Source Type: journals

Thrombospondins in the heart: potential functions in cardiac remodeling.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Cardiac remodeling after myocardial injury involves inflammation, angiogenesis, left ventricular hypertrophy and matrix remodeling. Thrombospondins (TSPs) belong to the group of matricellular proteins, which are non-structural extracellular matrix proteins that modulate cell-matrix interactions and cell function in injured tissues or tumors. They interact with different matrix and membrane-bound proteins due to their diverse functional domains. That the expression of TSPs strongly increases during cardiac stress or injury indicates an important role for them during cardiac remodeling. Recently, the protective propertie...
Source: Journal of Cell Communication and Signaling - October 1, 2009 Category: Molecular Biology Authors: Schellings MW, van Almen GC, Sage EH, Heymans S Tags: J Cell Commun Signal Source Type: journals

The role of osteopontin in inflammatory processes.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Osteopontin (OPN) is a matricellular protein that mediates diverse biological functions. OPN is involved in normal physiological processes and is implicated in the pathogenesis of a variety of disease states, including atherosclerosis, glomerulonephritis, cancer, and several chronic inflammatory diseases. Through interactions with several integrins, OPN mediates cell migration, adhesion, and survival in many cell types. OPN also functions as a Th1 cytokine, promotes cell-mediated immune responses, and plays a role in chronic inflammatory and autoimmune diseases. Besides its function in inflammation, OPN is also a regul...
Source: Journal of Cell Communication and Signaling - October 1, 2009 Category: Molecular Biology Authors: Lund SA, Giachelli CM, Scatena M Tags: J Cell Commun Signal Source Type: journals

Thrombopoietic-mesenchymal interaction that may facilitate both endochondral ossification and platelet maturation via CCN2.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
In this study, we initially pursued the possible origin of the CCN2 in platelets. First, we examined if the CCN2 in platelets was produced by megakaryocyte progenitors during differentiation. Unexpectedly, neither megakaryocytic CMK cells nor megakaryocytes that had differentiated from human haemopoietic stem cells in culture showed any detectable CCN2 gene expression or protein production. Together with the fact that no appreciable CCN2 was detected in megakaryocytes in vivo, these results suggest that megakaryocytes themselves do not produce CCN2. Next, we suspected that mesenchymal cells situated around megakaryocytes i...
Source: Journal of Cell Communication and Signaling - October 1, 2009 Category: Molecular Biology Authors: Sumiyoshi K, Kubota S, Furuta RA, Yasui K, Aoyama E, Kawaki H, Kawata K, Ohgawara T, Yamashiro T, Takigawa M Tags: J Cell Commun Signal Source Type: journals

Fibulin-5, an integrin-binding matricellular protein: its function in development and disease.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Interactions between the extracellular matrix (ECM) and cells are critical in embryonic development, tissue homeostasis, physiological remodeling, and tumorigenesis. Matricellular proteins, a group of ECM components, mediate cell-ECM interactions. One such molecule, Fibulin-5 is a 66-kDa glycoprotein secreted by various cell types, including vascular smooth muscle cells (SMCs), fibroblasts, and endothelial cells. Fibulin-5 contributes to the formation of elastic fibers by binding to structural components including tropoelastin and fibrillin-1, and to cross-linking enzymes, aiding elastic fiber assembly. Mice deficient ...
Source: Journal of Cell Communication and Signaling - October 1, 2009 Category: Molecular Biology Authors: Yanagisawa H, Schluterman MK, Brekken RA Tags: J Cell Commun Signal Source Type: journals

SPARC functions as an inhibitor of adipogenesis.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Adipogenesis, a key step in the pathogenesis of obesity, involves extensive ECM remodeling, changes in cell-ECM interactions, and cytoskeletal rearrangement. Matricellular proteins regulate cell-cell and cell-ECM interactions. Evidence in vivo and in vitro indicates that the prototypic matricellular protein, SPARC, inhibits adipogenesis and promotes osteoblastogenesis. Herein we discuss mechanisms underlying the inhibitory effect of SPARC on adipogenesis. SPARC enhances the Wnt/beta-catenin signaling pathway and regulates the expression and posttranslational modification of collagen. SPARC might drive preadipocytes awa...
Source: Journal of Cell Communication and Signaling - October 1, 2009 Category: Molecular Biology Authors: Nie J, Sage EH Tags: J Cell Commun Signal Source Type: journals

The many facets of the matricelluar protein periostin during cardiac development, remodeling, and pathophysiology.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Periostin is a member of a growing family of matricellular proteins, defined by their ability to interact with components of the extracellular milieu, and with receptors at the cell surface. Through these interactions, periostin has been shown to play a crucial role as a profibrogenic molecule during tissue morphogenesis. Tissues destined to become fibrous structures are dependent on cooperative interactions between periostin and its binding partners, whereas in its absence, these structures either totally or partially fail to become mature fibrous entities. Within the heart, fibrogenic differentiation is required for ...
Source: Journal of Cell Communication and Signaling - October 1, 2009 Category: Molecular Biology Authors: Norris RA, Moreno-Rodriguez R, Hoffman S, Markwald RR Tags: J Cell Commun Signal Source Type: journals

The role of SPARC in extracellular matrix assembly.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
SPARC is a collagen-binding matricellular protein. Expression of SPARC in adult tissues is frequently associated with excessive deposition of collagen and SPARC-null mice fail to generate a robust fibrotic response to a variety of stimuli. This review summarizes recent advancements in the characterization of the binding of SPARC to collagens and describes the results of studies that implicate a function for SPARC in the regulation of the assembly of basal lamina and fibrillar collagen in the ECM. Potential cellular mechanisms that underlie SPARC activity in ECM deposition are also explored. PMID: 19798598 [PubMed -...
Source: Journal of Cell Communication and Signaling - October 1, 2009 Category: Molecular Biology Authors: Bradshaw AD Tags: J Cell Commun Signal Source Type: journals

Thrombospondins function as regulators of angiogenesis.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Thrombospondins (TSPs) -1 and -2 were among the first protein inhibitors of angiogenesis to be identified, a property that was subsequently attributed to the interactions of sequences in their type I repeats with endothelial cell-surface receptors. The interactions of TSPs-1 and -2 with cell-surface receptors, proteases, growth factors, and other bioactive molecules, coupled with the absence of direct structural functions that can be attributed to these matrix proteins, qualify them for inclusion in the category of 'matricellular proteins'. The phenotypes of TSP-1, TSP-2, and double TSP-1/2-null mice confirm the roles ...
Source: Journal of Cell Communication and Signaling - October 1, 2009 Category: Molecular Biology Authors: Bornstein P Tags: J Cell Commun Signal Source Type: journals

Matricellular proteins: an overview.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
PMID: 19779848 [PubMed - as supplied by publisher] (Source: Journal of Cell Communication and Signaling)
Source: Journal of Cell Communication and Signaling - September 24, 2009 Category: Molecular Biology Authors: Bornstein P Tags: J Cell Commun Signal Source Type: journals

Getting to the heart of the matter: CCN2 plays a role in cardiomyocyte hypertrophy.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Connective tissue growth factor (CTGF/CCN2) is overexpressed in diabetes. Diabetic rats possess myocardial and cardiomyocyte hypertrophy. In a recent report, Wang and colleagues (Am J Physiol Cell Physiol. 2009 Jul 22. [Epub ahead of print]) show that CCN2 directly mediates cardiomyocyte hypertrophy as well as that induced by high glucose and fatty acid. CCN2 acted via the TrkA receptor. These data are the subject of this commentary, and emphasize that CCN2 may be an excellent target for therapy in diabetes. PMID: 19701807 [PubMed - as supplied by publisher] (Source: Journal of Cell Communication and Signaling)
Source: Journal of Cell Communication and Signaling - August 23, 2009 Category: Molecular Biology Authors: Leask A Tags: J Cell Commun Signal Source Type: journals

CCN3 and bone marrow cells.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
CCN3 expression was observed in a broad variety of tissues from the early stage of development. However, a kind of loss of function in mice (CCN3 del VWC domain -/-) demonstrated mild abnormality, which indicates that CCN3 may not be critical for the normal embryogenesis as a single gene. The importance of CCN3 in bone marrow environment becomes to be recognized by the studies of hematopoietic stem cells and Chronic Myeloid Leukemia cells. CCN3 expression in bone marrow has been denied by several investigations, but we found CCN3 positive stromal and hematopoietic cells at bone extremities with a new antibody although ...
Source: Journal of Cell Communication and Signaling - July 22, 2009 Category: Molecular Biology Authors: Katsube KI, Ichikawa S, Katsuki Y, Kihara T, Terai M, Lau LF, Tamamura Y, Takeda S, Umezawa A, Sakamoto K, Yamaguchi A Tags: J Cell Commun Signal Source Type: journals

CCN3: a key growth regulator in Chronic Myeloid Leukaemia.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
This study shows that CCN3 is an important growth regulator in haematopoiesis, abrogation of CCN3 expression enhances BCR-ABL dependent leukaemogenesis. CCN3 restores growth regulation, regains sensitivity to the induction of apoptosis and enhances imatinib cell kill in CML cells. CCN3 may provide an additional therapeutic strategy in the management of CML. PMID: 19623482 [PubMed - as supplied by publisher] (Source: Journal of Cell Communication and Signaling)
Source: Journal of Cell Communication and Signaling - July 21, 2009 Category: Molecular Biology Authors: McCallum L, Lu W, Price S, Lazar N, Perbal B, Irvine AE Tags: J Cell Commun Signal Source Type: journals

Periostin localizes to cells in normal skin, but is associated with the extracellular matrix during wound repair.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Epidermal tissue repair represents a complex series of temporal and dynamic events resulting in wound closure. Matricellular proteins, not normally expressed in quiescent adult tissues, play a pivotal role in wound repair and associated extracellular matrix remodeling by modulating the adhesion, migration, intracellular signaling, and gene expression of inflammatory cells, pericytes, fibroblasts and keratinocytes. Several matricellular proteins show temporal expression during dermal wound repair, but the expression pattern of the recently identified matricellular protein, periostin, has not yet been characterized. The ...
Source: Journal of Cell Communication and Signaling - June 18, 2009 Category: Molecular Biology Authors: Jackson-Boeters L, Wen W, Hamilton DW Tags: J Cell Commun Signal Source Type: journals

Yin and Yang: CCN3 inhibits the pro-fibrotic effects of CCN2.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Fibrotic disease is a significant cause of mortality. CCN2 (connective tissue growth factor [CTGF]), a member of the CCN family of matricellular proteins, plays a significant role in driving the fibrogenic effects of cytokines such as transforming growth factor beta (TGFbeta). It has been proposed that other members of the CCN family can either promote or antagonize the action of CCN2, depending on the context. A recent elegant study published by Bruce Riser and colleagues (Am J Pathol. 174:1725-34, 2009) illustrates that CCN3 (nov) antagonizes the fibrogenic effects of CCN2. This paper, the subject of this commentary,...
Source: Journal of Cell Communication and Signaling - May 28, 2009 Category: Molecular Biology Authors: Leask A Tags: J Cell Commun Signal Source Type: journals

Normal growth and development in mice over-expressing the CCN family member WISP3.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Loss-of-function mutations in the gene WISP3 cause the autosomal recessive human skeletal disease Progressive Pseudorheumatoid Dysplasia, whereas mice with knockout mutations of Wisp3 have no phenotype. The lack of a phenotype in the Wisp3 knockout mice has constrained studies of the protein's in vivo function. Over-expression experiments in zebrafish indicated that WISP3 may function as a BMP and Wnt signaling modulator. To determine whether these biologic activities are retained in mice, we created two strains of transgenic mice that over-express WISP3 in a broad array of tissues. Despite strong and persistent protei...
Source: Journal of Cell Communication and Signaling - April 28, 2009 Category: Molecular Biology Authors: Nakamura Y, Cui Y, Fernando C, Kutz WE, Warman ML Tags: J Cell Commun Signal Source Type: journals

Alternative splicing of CCN mRNAs .... it has been upon us.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Variant CCN proteins have been identified over the past decade in several normal and pathological situations. The production of CCN truncated proteins have been reported in the case of CCN2(ctgf), CCN3(nov), CCN4(wisp-1) and CCN6(wisp-3). Furthermore, the natural CCN5 is known to miss the C-terminal domain that is present in all other members of the CCN family of proteins. In spite of compelling evidence that assign important biological activities to these truncated CCN variants, their potential regulatory functions have only recently begun to be widely accepted. The report of CCN1(cyr61) intron 3 retention in breast c...
Source: Journal of Cell Communication and Signaling - April 27, 2009 Category: Molecular Biology Authors: Perbal B Tags: J Cell Commun Signal Source Type: journals

What's in an intron? CCN1 mRNA splicing in cancer.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
The CCN family of matricellular signaling regulators shares a common domain structure. Variants of individual CCN proteins exist, which contain different combinations of these domains. Although mRNA splicing is likely to play a key role on CCN biology, this hypothesis has not been thoroughly tested. In a recent report, Hirschfeld and colleagues (Cancer Res 69:2082-90, 2009), show that CCN1 (cyr61) mRNA is normally present in a form in which intron 3 is retained. In cancers, or upon hypoxia, intron 3 is removed resulting in the appearance of CCN1 protein. The significance of this paper is discussed. PMID: 19381874 [...
Source: Journal of Cell Communication and Signaling - April 20, 2009 Category: Molecular Biology Authors: Leask A Tags: J Cell Commun Signal Source Type: journals

A rapid and sensitive method for measuring cell adhesion.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
We have adapted the CyQuant(R) assay to provide a simple, rapid, sensitive and highly reproducible method for measuring cell adhesion. The modified CyQuant(R) assay eliminates the requirement for labour intensive fluorescent labelling protocols prior to experimentation and has the sensitivity to measure small numbers (>1000) of adherent cells. PMID: 19370401 [PubMed - as supplied by publisher] (Source: Journal of Cell Communication and Signaling)
Source: Journal of Cell Communication and Signaling - April 15, 2009 Category: Molecular Biology Authors: Lu W, McCallum L, Irvine AE Tags: J Cell Commun Signal Source Type: journals

Wnt 10b activates the CCN2 promoter in NIH 3T3 fibroblasts through the Smad response element.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
In this report, we map the Wnt10b response element in the CCN2 minimal promoter to the previously identified Smad response element. These results suggest that Wnts may cross-talk with the Smad signaling pathway to induce fibrotic responses in fibroblasts. PMID: 19353303 [PubMed - as supplied by publisher] (Source: Journal of Cell Communication and Signaling)
Source: Journal of Cell Communication and Signaling - April 8, 2009 Category: Molecular Biology Authors: Chen S, Leask A Tags: J Cell Commun Signal Source Type: journals

Global expression profiling reveals regulation of CTGF/CCN2 during lactogenic differentiation.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Mammary epithelial cells go through a series of developmental changes during pregnancy and lactation including proliferation, differentiation, secretion and apoptosis. HC11 mouse mammary epithelial cells, which undergo lactogen-induced differentiation in cell culture, were used to follow the changes in gene expression during this process. The expression profiles of over 20,000 genes were compared in HC11 cells undergoing lactogenic differentiation to non-differentiated cells using DNA microarray analysis. Greater than two fold changes were detected in 998 genes in the differentiated cells versus growth controls. Severa...
Source: Journal of Cell Communication and Signaling - April 8, 2009 Category: Molecular Biology Authors: Wang W, Jose C, Kenney N, Morrison B, Cutler ML Tags: J Cell Commun Signal Source Type: journals

Expression of CCN family of genes in human skin in vivo and alterations by solar-simulated ultraviolet irradiation.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
The CCN family of proteins is involved in diverse biological functions such as cell growth, adhesion, migration, angiogenesis, and regulation of extracellular matrix. We have investigated expression of CCN family genes and alternations induced by solar-simulated ultraviolet irradiation in human skin in vivo. Transcripts of all six CCN genes were expressed in human skin in vivo. CCN5 was most abundantly expressed followed by CCN2>CCN3>CCN1>CCN4>CCN6. Solar-simulated ultraviolet irradiation increased mRNA expression of CCN1 and CCN2. In contrast, mRNA levels of CCN3, CCN4, CCN5, and CCN6, were reduced. Knowle...
Source: Journal of Cell Communication and Signaling - March 25, 2009 Category: Molecular Biology Authors: Quan T, Shin S, Qin Z, Fisher GJ Tags: J Cell Commun Signal Source Type: journals

Strategies for blocking the fibrogenic actions of connective tissue growth factor (CCN2): From pharmacological inhibition in vitro to targeted siRNA therapy in vivo.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Connective tissue growth factor (CCN2) is a major pro-fibrotic factor that frequently acts downstream of transforming growth factor beta (TGF-beta)-mediated fibrogenic pathways. Much of our knowledge of CCN2 in fibrosis has come from studies in which its production or activity have been experimentally attenuated. These studies, performed both in vitro and in animal models, have demonstrated the utility of pharmacological inhibitors (e.g. tumor necrosis factor alpha (TNF-alpha), prostaglandins, peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists, statins, kinase inhibitors), neutralizing antibodies, a...
Source: Journal of Cell Communication and Signaling - March 18, 2009 Category: Molecular Biology Authors: Brigstock DR Tags: J Cell Commun Signal Source Type: journals

Death of a tumor: targeting CCN in pancreatic cancer.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
This report briefly summarizes these findings. PMID: 19267221 [PubMed - as supplied by publisher] (Source: Journal of Cell Communication and Signaling)
Source: Journal of Cell Communication and Signaling - March 8, 2009 Category: Molecular Biology Authors: Leask A Tags: J Cell Commun Signal Source Type: journals

Trial by CCN2: a standardized test for fibroproliferative disease?email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
A major issue concerning clinical trials is the availability of standardized assays to evaluate drug efficacy. Ideally, such assays should test the effect of a putative drug on the expression of a biomarker in biological fluids. In a recent study by Kuiper et al. (PLOS One, 3(7): e2675). The relative levels of vascular endothelial growth factor (VEGF) and CCN2 (connective tissue growth factor [CTGF]) were examined in proliferative diabetic retinopathy (PDR). This paper is the subject of this commentary. PMID: 19266315 [PubMed - as supplied by publisher] (Source: Journal of Cell Communication and Signaling)
Source: Journal of Cell Communication and Signaling - March 7, 2009 Category: Molecular Biology Authors: Leask A Tags: J Cell Commun Signal Source Type: journals

Connective tissue growth factor(CCN2), a pathogenic factor in diabetic nephropathy. What does it do? How does it do it?email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Connective tissue growth factor (CTGF/CCN2) is a member of the CCN family of matricellular proteins. Its expression is induced by a number of factors including TGF-beta. It has been associated with fibrosis in various tissues including the kidney. Diabetic nephropathy (DN) develops in about 30% of patients with diabetes and is characterized by thickening of renal basement membranes, fibrosis in the glomerulus (glomerulosclerosis), tubular atrophy and interstitial fibrosis, all of which compromise kidney function. This review examines changes in CTGF expression in the kidney in DN, the effects they have on glomerular me...
Source: Journal of Cell Communication and Signaling - February 14, 2009 Category: Molecular Biology Authors: Mason RM Tags: J Cell Commun Signal Source Type: journals

Connective tissue growth factor (CTGF, CCN2) gene regulation: a potent clinical bio-marker of fibroproliferative disease?email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
The CCN (cyr61, ctgf, nov) family of modular proteins regulate diverse biological affects including cell adhesion, matrix production, tissue remodelling, proliferation and differentiation. Recent targeted gene disruption studies have demonstrated the CCN family to be developmentally essential for chondrogenesis, osteogenesis and angiogenesis. CCN2 is induced by agents such as angiotensin II, endothelin-1, glucocorticoids, HGF, TGFbeta, and VEGF, and by hypoxia and biomechanical and shear stress. Dysregulated expression of CCN2 has also been widely documented in many fibroproliferative diseases. This mini-review will fo...
Source: Journal of Cell Communication and Signaling - January 21, 2009 Category: Molecular Biology Authors: Leask A, Parapuram SK, Shi-Wen X, Abraham DJ Tags: J Cell Commun Signal Source Type: journals

Report on the fifth international workshop on the CCN family of genes.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
The Fifth International Workshop on the CCN Family of Genes was held in Toronto October 18-22, 2008. This bi-annual workshop provides a unique opportunity for the presentation and discussion of cutting edge research in the CCN field. The CCN family members have emerged as extracellular matrix associated proteins which play a crucial role in cardiovascular and skeletal development, fibrosis and cancer. Significant progress has been made in the development of model systems to tease apart the CCN signalling pathways in these systems. Results presented at the conference suggest that targeting these pathways now shows real ...
Source: Journal of Cell Communication and Signaling - January 21, 2009 Category: Molecular Biology Authors: Irvine AE, Perbal B, Yeger H Tags: J Cell Commun Signal Source Type: journals

Fifth International Workshop on the CCN Family of Genes: Abstracts and Posters October 18-22, 2008.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Authors: PMID: 19152120 [PubMed - as supplied by publisher] (Source: Journal of Cell Communication and Signaling)
Source: Journal of Cell Communication and Signaling - January 19, 2009 Category: Molecular Biology Tags: J Cell Commun Signal Source Type: journals

Using Caenorhabditis elegans as a model organism for evaluating extracellular signal-regulated kinase docking domain inhibitors.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
We have recently identified several novel ATP-independent inhibitors that target the extracellular signal-regulated kinase-2 (ERK2) protein and inhibit substrate phosphorylation. To further characterize these compounds, we describe the use of C. elegans as a model organism. C. elegans is recognized as a versatile and cost effective model for use in drug development. These studies take advantage of the well characterized process of vulva development and egg laying, which requires MPK-1, the homolog to human ERK2. It is shown that treatment of C. elegans eggs or larvae prior to vulva formation with a previously identifie...
Source: Journal of Cell Communication and Signaling - December 23, 2008 Category: Molecular Biology Authors: Chen F, Mackerell AD, Luo Y, Shapiro P Tags: J Cell Commun Signal Source Type: journals

Matricellular CCN proteins.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
We kindly invite you to consider the Journal of Cell Communication and Signaling (JCCS) as a media for publication of your research and participate in promoting JCCS as an important platform for disseminating new results in the fields of cell signaling. PMID: 19067237 [PubMed - as supplied by publisher] (Source: Journal of Cell Communication and Signaling)
Source: Journal of Cell Communication and Signaling - December 9, 2008 Category: Molecular Biology Authors: Perbal B Tags: J Cell Commun Signal Source Type: journals

Expression and function of alphabeta1 integrins in pancretic beta (INS-1) cells.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Integrin-extracellular matrix interactions are important determinants of beta cell behaviours. The beta1 integrin is a well-known regulator of beta cell activities; however, little is known of its associated alpha subunits. In the present study, alphabeta1 integrin expression was examined in the rat insulinoma cell line (INS-1) to identify their role in beta cell survival and function. Seven alpha subunits associated with beta1 integrin were identified, including alpha1-6 and alphaV. Among these heterodimers, alpha3beta1 was most highly expressed. Common ligands for the alpha3beta1 integrin, including fibronectin, lami...
Source: Journal of Cell Communication and Signaling - November 21, 2008 Category: Molecular Biology Authors: Krishnamurthy M, Li J, Al-Masri M, Wang R Tags: J Cell Commun Signal Source Type: journals

The Notochord, Notochordal cell and CTGF/CCN-2: ongoing activity from development through maturation.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
The growth regulating factor CTGF/CCN-2 is an integral factor in growth and development, connective tissue maintenance, wound repair and cell cycle regulation. It has recently been reported that CTGF/CCN-2 is involved in very early development having been detected in early notochord formation in zebrafish using CTGF/CCN-2 promoter-driven green fluorescent protein (GFP) plasmids. In these studies fluorescence was detected early in the developing embryos, a finding of considerable significance in that CTGF/CCN-2 deficient mutant mice die early after birth due to severe cartilage and skeletal dysplasia and respiratory fai...
Source: Journal of Cell Communication and Signaling - November 12, 2008 Category: Molecular Biology Authors: Erwin WM Tags: J Cell Commun Signal Source Type: journals

The skinny on CCN2.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
The CCN family of matricellular proteins directly or indirectly affects development and differentiation. A recent report written by Tan and colleagues (Am J Physiol Cell Physiol 295: C740-C751 2008) shows that CCN2 inhibits adipocyte differentiation. This commentary summarizes these observations. PMID: 18991022 [PubMed - as supplied by publisher] (Source: Journal of Cell Communication and Signaling)
Source: Journal of Cell Communication and Signaling - November 8, 2008 Category: Molecular Biology Authors: Leask A Tags: J Cell Commun Signal Source Type: journals

Regulation of CCN2 mRNA expression and promoter activity in activated hepatic stellate cells.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
The matricellular protein connective tissue growth factor (CCN2) is considered a faithful marker of fibroblast activation in wound healing and in fibrosis. CCN2 is induced during activation of hepatic stellate cells (HSC). Here, we investigate the molecular basis of CCN2 gene expression in HSC. Fluoroscence activated cell sorting was used to investigate CCN2 expression in HSC in vivo in mice treated with CCl(4). CCN2 and TGF-beta mRNA expression were assessed by polymerase chain reaction as a function of culture-induced activation of HSC. CCN2 promoter/reporter constructs were used to map cis-acting elements required f...
Source: Journal of Cell Communication and Signaling - September 17, 2008 Category: Molecular Biology Authors: Leask A, Chen S, Pala D, Brigstock DR Tags: J Cell Commun Signal Source Type: journals

CCN3: Doctor Jekyll and Mister Hyde.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
CCN proteins are key regulators of signaling pathways that are essential for the control of normal life, from birth to death. As such, they make use of their unique mosaic structure to interact with several other regulatory proteins and ligands that control the fate of living cells. The various functions attributed to the CCN proteins may sometimes appear contradictory, but this situation reflects the complexity of the multimolecular scaffolds in which CCN proteins are engaged and the critical impact of the microenvironment that dictates the bioavailability of the elementary building blocks. CCN3 is one of the best exa...
Source: Journal of Cell Communication and Signaling - September 12, 2008 Category: Molecular Biology Authors: Perbal B Tags: J Cell Commun Signal Source Type: journals

CCN2 YAPs at cancer.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
This report briefly summarizes these findings. PMID: 18766468 [PubMed - as supplied by publisher] (Source: Journal of Cell Communication and Signaling)
Source: Journal of Cell Communication and Signaling - September 3, 2008 Category: Molecular Biology Authors: Leask A Tags: J Cell Commun Signal Source Type: journals

Enzymes used in molecular biology: a useful guide.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Since molecular cloning has become routine laboratory technique, manufacturers offer countless sources of enzymes to generate and manipulate nucleic acids. Thus, selecting the appropriate enzyme for a specific task may seem difficult to the novice. This review aims at providing the readers with some cues for understanding the function and specificities of the different sources of polymerases, ligases, nucleases, phosphatases, methylases, and topoisomerases used for molecular cloning. We provide a description of the most commonly used enzymes of each group, and explain their properties and mechanism of action. By pointi...
Source: Journal of Cell Communication and Signaling - September 3, 2008 Category: Molecular Biology Authors: Rittié L, Perbal B Tags: J Cell Commun Signal Source Type: journals

The Starbuck stops here: it's a Smad world.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
A recent study by Gressner and colleagues suggested caffeine may block CCN2 expression in hepatic cells. This commentary briefly summarizes these observations. PMID: 18649015 [PubMed - as supplied by publisher] (Source: Journal of Cell Communication and Signaling)
Source: Journal of Cell Communication and Signaling - July 23, 2008 Category: Molecular Biology Authors: Leask A Tags: J Cell Commun Signal Source Type: journals