The pleckstrin homology domain of phospholipase D1 accelerates EGFR endocytosis by increasing the expression of the Rab5 effector, rabaptin-5.
Abstract
Endocytosis is differentially regulated by hypoxia-inducible factor-1α (HIF-1α) and phospholipase D (PLD). However, the relationship between HIF-1α and PLD in endocytosis is unknown. HIF-1α is degraded through the prolyl hydroxylase (PHD)/von Hippel-Lindau (VHL) ubiquitination pathway in an oxygen-dependent manner. Here, we show that PLD1 recovers the decrease in epidermal growth factor receptor (EGFR) endocytosis induced by HIF-1α independent of lipase activity via the Rab5-mediated endosome fusion pathway. EGF-induced interaction of PLD1 with HIF-1α, PHD and VHL may contribute to EGFR endo...
Source: exp Mol Med - December 19, 2015 Category: Molecular Biology Authors: Park MH, Choi KY, Min do S Tags: Exp Mol Med Source Type: research
The Wnt/β-catenin signaling pathway regulates the development of airway remodeling in patients with asthma.
In this study, we investigated the roles of Wnt/β-catenin signaling in airway remodeling in patients with asthma. Wnt7a mRNA expression was prominent in induced sputum from patients with asthma compared with that from healthy controls. Next, we induced a chronic asthma mouse model with airway remodeling features, including subepithelial fibrosis and airway smooth muscle hyperplasia. Higher expression of Wnt family proteins and β-catenin was detected in the lung tissue of mice with chronic asthma compared to control mice. Blocking β-catenin expression with a specific siRNA attenuated airway inflammation and airway remode...
Source: exp Mol Med - December 16, 2015 Category: Molecular Biology Authors: Kwak HJ, Park DW, Seo JY, Moon JY, Kim TH, Sohn JW, Shin DH, Yoon HJ, Park SS, Kim SH Tags: Exp Mol Med Source Type: research
Crosstalk between FLS and chondrocytes is regulated by HIF-2α-mediated cytokines in arthritis.
This study broadens our understanding of the possible regulatory mechanisms underlying the crosstalk between the synovium and cartilage in the presence of HIF-2α, and may suggest potential new anti-arthritis therapies.
PMID: 26642431 [PubMed - in process] (Source: exp Mol Med)
Source: exp Mol Med - December 10, 2015 Category: Molecular Biology Authors: Huh YH, Lee G, Song WH, Koh JT, Ryu JH Tags: Exp Mol Med Source Type: research
Adseverin mediates RANKL-induced osteoclastogenesis by regulating NFATc1.
Abstract
Adseverin is a Ca(2+)-dependent actin filament-severing protein that has been reported to regulate exocytosis via rearrangements of the actin cytoskeleton in secretory cells. However, the role of adseverin in bone cells has not yet been well characterized. Here, we investigated the role of adseverin in osteoclastogenesis using primary osteoclast precursor cells. Adseverin expression was upregulated during RANKL (receptor activator of nuclear factor-κB ligand)-induced osteoclast differentiation. Moreover, genetic silencing of adseverin decreased the number of osteoclasts generated by RANKL. Adseve...
Source: exp Mol Med - December 10, 2015 Category: Molecular Biology Authors: Song MK, Lee ZH, Kim HH Tags: Exp Mol Med Source Type: research
Biological characteristics of tracheal smooth muscle cells regulated by NK-1R in asthmatic rat with airway remodeling.
This study aims to investigate the biological characteristic changes of infant rat tracheal smooth muscle cells in asthma airway remodeling and the impact of NK-1R on the mechanism. Ovalbumin (OVA) was used to excited juvenile SD rats by 8 w. Immunofluorescence, MTT assay, transwell chambers, real time quantitative PCR, Western blot and other methods were used to observe the proliferation, migration, synthesis and secretion changes of infant airway remodeling in rat tracheal smooth muscle cell and the Neurokinin 1 receptor (NK-1R) expression. 1. NK-1R mRNA, protein expression of airway smooth muscle cell (ASMC) of each ast...
Source: exp Mol Med - December 4, 2015 Category: Molecular Biology Authors: Wei B, Liu Y, Yue X, Li Y, Shang Y Tags: Int J Clin Exp Med Source Type: research
Phospholipase D2 promotes degradation of hypoxia-inducible factor-1α independent of lipase activity.
Abstract
Hypoxia-inducible factor-1α (HIF-1α) is a key transcriptional mediator that coordinates the expression of various genes involved in tumorigenesis in response to changes in oxygen tension. The stability of HIF-1α protein is determined by oxygen-dependent prolyl hydroxylation, which is required for binding of the von Hippel-Lindau protein (VHL), the recognition component of an E3 ubiquitin ligase that targets HIF-1α for ubiquitination and degradation. Here, we demonstrate that PLD2 protein itself interacts with HIF-1α, prolyl hydroxylase (PHD) and VHL to promote degradation of HIF-1α via the p...
Source: exp Mol Med - November 28, 2015 Category: Molecular Biology Authors: Park MH, Bae SS, Choi KY, Min DS Tags: Exp Mol Med Source Type: research
Clinicopathological values of NBS1 and DNA damage response genes in epithelial ovarian cancers.
Abstract
Epithelial ovarian cancers (EOCs) are highly lethal gynecological malignancies with a high recurrence rate. Therefore, developing prognostic markers for recurrence after chemotherapy is crucial for the treatment of ovarian cancers. As ovarian cancers frequently respond to DNA-damaging agents, we assessed the clinicopathological significance of key double-strand DNA break (DSB) repair genes, including BRCA1, BRCA2, BARD1, ATM, RAD51 and NBS1 in EOC cell lines and paraffin-embedded tissue sections from 140 EOC patients treated with cytoreductive surgery, followed by platinum-based chemotherapy. Thes...
Source: exp Mol Med - November 21, 2015 Category: Molecular Biology Authors: Lee YK, Park NH, Lee H Tags: Exp Mol Med Source Type: research
Serum amyloid A inhibits RANKL-induced osteoclast formation.
Abstract
When mouse bone marrow-derived macrophages were stimulated with serum amyloid A (SAA), which is a major acute-phase protein, there was strong inhibition of osteoclast formation induced by the receptor activator of nuclear factor kappaB ligand. SAA not only markedly blocked the expression of several osteoclast-associated genes (TNF receptor-associated factor 6 and osteoclast-associated receptor) but also strongly induced the expression of negative regulators (MafB and interferon regulatory factor 8). Moreover, SAA decreased c-fms expression on the cell surface via shedding of the c-fms extracellula...
Source: exp Mol Med - November 16, 2015 Category: Molecular Biology Authors: Oh E, Lee HY, Kim HJ, Park YJ, Seo JK, Park JS, Bae YS Tags: Exp Mol Med Source Type: research
Clinical implications of proliferation activity in T1 or T2 male gastric cancer patients.
Abstract
Proliferation activity has already been established as a prognostic marker or as a marker for anticancer drug sensitivity. In gastric cancer, however, the prognostic significance of proliferation activity is still being debated. Several studies evaluating proliferation activity using Ki-67 have shown controversial results in terms of the relationship between proliferation activity and overall survival (OS) or drug sensitivity in gastric cancer patients. Because cytoskeleton-associated protein 2 (CKAP2) staining has recently been introduced as a marker of proliferation activity, we analyzed 437 gas...
Source: exp Mol Med - November 9, 2015 Category: Molecular Biology Authors: Kim YW, Eom BW, Kook MC, Kim HS, Kim MK, Hwang HL, Chandra V, Poojan S, Song Y, Koh JS, Bae CD, Ro J, Hong KM Tags: Exp Mol Med Source Type: research
The Role of Human Chorionic Gonadotropin as Tumor Marker: Biochemical and Clinical Aspects.
Abstract
Tumor markers are biological substances that are produced/released mainly by malignant tumor cells, enter the circulation in detectable amounts and are potential indicators of the presence of a tumor. The most useful biochemical markers are the tumor-specific molecules, i.e., receptors, enzymes, hormones, growth factors or biological response modifiers that are specifically produced by tumor cells and not, or minimally, by the normal counterpart (Richard et al. Principles and practice of gynecologic oncology. Wolters Kluwer Health, Philadelphia, 2009). Based on their specificity and sensitivity in...
Source: exp Mol Med - November 6, 2015 Category: Molecular Biology Authors: Sisinni L, Landriscina M Tags: Adv Exp Med Biol Source Type: research
Caveolin-1 regulates osteoclast differentiation by suppressing cFms degradation.
Abstract
Caveolae are flask-shaped cell-surface membranes, which consist of cholesterol, sphingolipids and caveolin proteins. In a microarray analysis, we found that caveolin-1 (Cav-1) was upregulated by receptor activator of NFκB ligand (RANKL), the osteoclast differentiation factor. Silencing of Cav-1 inhibited osteoclastogenesis and also decreased the activation of mitogen-activated protein kinase and the induction of NFATc1 by RANKL. Cav-1 knockdown suppressed the expression of cFms and RANK, two major receptors for osteoclastogenesis. Interestingly, cFms expression was decreased only at the protein l...
Source: exp Mol Med - November 1, 2015 Category: Molecular Biology Authors: Lee YD, Yoon SH, Ji E, Kim HH Tags: Exp Mol Med Source Type: research
Pycnogenol attenuates atherosclerosis by regulating lipid metabolism through the TLR4-NF-κB pathway.
Abstract
Atherosclerosis is a leading cause of death worldwide and is characterized by lipid-laden foam cell formation. Recently, pycnogenol (PYC) has drawn much attention because of its prominent effect on cardiovascular disease (CVD). However, its protective effect against atherosclerosis and the underlying mechanism remains undefined. Here PYC treatment reduced areas of plaque and lipid deposition in atherosclerotic mice, concomitant with decreases in total cholesterol and triglyceride levels and increases in HDL cholesterol levels, indicating a potential antiatherosclerotic effect of PYC through the re...
Source: exp Mol Med - October 25, 2015 Category: Molecular Biology Authors: Luo H, Wang J, Qiao C, Ma N, Liu D, Zhang W Tags: Exp Mol Med Source Type: research
Rac-mediated actin remodeling and myosin II are involved in KATP channel trafficking in pancreatic β-cells.
Abstract
AMP-activated protein kinase (AMPK) is a metabolic sensor activated during metabolic stress and it regulates various enzymes and cellular processes to maintain metabolic homeostasis. We previously reported that activation of AMPK by glucose deprivation (GD) and leptin increases KATP currents by increasing the surface levels of KATP channel proteins in pancreatic β-cells. Here, we show that the signaling mechanisms that mediate actin cytoskeleton remodeling are closely associated with AMPK-induced KATP channel trafficking. Using F-actin staining with Alexa 633-conjugated phalloidin, we observed th...
Source: exp Mol Med - October 17, 2015 Category: Molecular Biology Authors: Han YE, Lim A, Park SH, Chang S, Lee SH, Ho WK Tags: Exp Mol Med Source Type: research
miR-139 modulates MCPIP1/IL-6 expression and induces apoptosis in human OA chondrocytes.
Abstract
IL-6 is an inflammatory cytokine and its overexpression plays an important role in osteoarthritis (OA) pathogenesis. Expression of IL-6 is regulated post-transcriptionally by MCPIP1. The 3' untranslated region (UTR) of MCPIP1 mRNA harbors a miR-139 'seed sequence', therefore we examined the post-transcriptional regulation of MCPIP1 by miR-139 and its impact on IL-6 expression in OA chondrocytes. Expression of miR-139 was found to be high in the damaged portion of the OA cartilage compared with unaffected cartilage from the same patient and was also induced by IL-1β in OA chondrocytes. Inhibition ...
Source: exp Mol Med - October 10, 2015 Category: Molecular Biology Authors: Makki MS, Haqqi TM Tags: Exp Mol Med Source Type: research
Murine Sca1(+)Lin(-) bone marrow contains an endodermal precursor population that differentiates into hepatocytes.
In this study, we established an efficient in vitro culture method for differentiation of functioning hepatocytes from murine lineage-negative bone marrow cells. These cells reduced liver damage and incorporated into hepatic parenchyma in two independent hepatic injury models. Our simple and efficient in vitro protocol for endodermal precursor cell survival and expansion enabled us to identify these cells as existing in Sca1(+) subpopulations of lineage-negative bone marrow cells. The endodermal precursor cells followed a sequential developmental pathway that included endodermal cells and hepatocyte precursor cells, which ...
Source: exp Mol Med - October 5, 2015 Category: Molecular Biology Authors: Oh K, Shon SY, Seo MW, Lee HM, Oh JE, Choi EY, Lee DS, Park KS Tags: Exp Mol Med Source Type: research
