Platelet-derived growth factor receptor-{alpha} and Ras-related C3 botulinum toxin substrate-1 regulate mechano-responsiveness of lung fibroblasts
Platelet-derived growth factor (PDGF)-A, which only signals through PDGF-receptor-α (PDGFR-α), is required for secondary alveolar septal formation. Although PDGFR-α distinguishes mesenchymal progenitor cells during the saccular stage, PDGFR-α-expressing alveolar cells persist through adulthood. PDGF-A sustains proliferation, limits apoptosis, and maintains α-smooth muscle actin (α-SMA)-containing alveolar cells, which congregate at the alveolar entry ring at postnatal day (P)12. PDGFR-α-expressing, α-SMA-containing alveolar cells redistribute in the elongating septum, suggest...
Source: AJP: Lung Cellular and Molecular Physiology - December 1, 2017 Category: Respiratory Medicine Authors: McGowan, S. E., McCoy, D. M. Tags: RESEARCH ARTICLE Source Type: research

IPF lung fibroblasts have a senescent phenotype
The mechanisms of aging that are involved in the development of idiopathic pulmonary fibrosis (IPF) are still unclear. Although it has been hypothesized that the proliferation and activation of human lung fibroblasts (hLFs) are essential in IPF, no studies have assessed how this process works in an aging lung. Our goal was to elucidate if there were age-related changes on primary hLFs isolated from IPF lungs compared with age-matched controls. We investigated several hallmarks of aging in hLFs from IPF patients and age-matched controls. IPF hLFs have increased cellular senescence with higher expression of β-galactosid...
Source: AJP: Lung Cellular and Molecular Physiology - December 1, 2017 Category: Respiratory Medicine Authors: Alvarez, D., Cardenes, N., Sellares, J., Bueno, M., Corey, C., Hanumanthu, V. S., Peng, Y., DCunha, H., Sembrat, J., Nouraie, M., Shanker, S., Caufield, C., Shiva, S., Armanios, M., Mora, A. L., Rojas, M. Tags: RESEARCH ARTICLE Source Type: research

Element-based prognostics of occupational pneumoconiosis using micro-proton-induced X-ray emission analysis
Pneumoconiosis is an occupational disease accompanied by long-term lung impairment, for which prediction of prognosis is poorly understood because of the complexity of the inhaled particles. Micro-proton-induced X-ray emission (micro-PIXE) analysis, which is advantageous for high-sensitivity, two-dimensional element mapping of lung tissues, was used to investigate element-based predictive factors of prognosis in Chinese patients with welder’s and coal miner’s pneumoconiosis. Chest radiographs and lung function tests showed that most of the coal miners deteriorated, whereas symptoms in some welders were alleviat...
Source: AJP: Lung Cellular and Molecular Physiology - December 1, 2017 Category: Respiratory Medicine Authors: He, X., Shen, H., Chen, Z., Rong, C., Ren, M., Hou, L., Wu, C., Mao, L., Lu, Q., Su, B. Tags: RESEARCH ARTICLE Source Type: research

Recent advances in our understanding of the mechanisms of late lung development and bronchopulmonary dysplasia
The objective of lung development is to generate an organ of gas exchange that provides both a thin gas diffusion barrier and a large gas diffusion surface area, which concomitantly generates a steep gas diffusion concentration gradient. As such, the lung is perfectly structured to undertake the function of gas exchange: a large number of small alveoli provide extensive surface area within the limited volume of the lung, and a delicate alveolo-capillary barrier brings circulating blood into close proximity to the inspired air. Efficient movement of inspired air and circulating blood through the conducting airways and condu...
Source: AJP: Lung Cellular and Molecular Physiology - December 1, 2017 Category: Respiratory Medicine Authors: Surate Solaligue, D. E., Rodriguez-Castillo, J. A., Ahlbrecht, K., Morty, R. E. Tags: REVIEW Source Type: research

Epigenetic changes by DNA methylation in chronic and intermittent hypoxia
This article presents a brief update on emerging evidence suggesting that changes in DNA methylation contribute to pathologies caused by chronic IH and potentially mediate adaptations to chronic sustained hypoxia by affecting the hypoxia-inducible factor (HIF) signaling pathway. (Source: AJP: Lung Cellular and Molecular Physiology)
Source: AJP: Lung Cellular and Molecular Physiology - December 1, 2017 Category: Respiratory Medicine Authors: Nanduri, J., Semenza, G. L., Prabhakar, N. R. Tags: REVIEW Source Type: research

Childhood tolerance of severe influenza: a mortality analysis in mice
During the 1918 influenza pandemic, children experienced substantially lower mortality than adults, a striking but unexplained finding. Whether this was due to enhanced resistance (reduced virus load) or better tolerance (reduced impact of infection) has not been defined. We found that prepubertal mice infected with H1N1 influenza virus also showed greater survival than infected pubertal mice, despite similar virus loads. Transcriptome profiling of infected lungs identified estrogen as a regulator of susceptibility in both sexes and also linked better survival to late expression of IL-1β. Blocking puberty with gonadec...
Source: AJP: Lung Cellular and Molecular Physiology - December 1, 2017 Category: Respiratory Medicine Authors: Suber, F., Kobzik, L. Tags: RESEARCH ARTICLE Source Type: research

Versican is produced by Trif- and type I interferon-dependent signaling in macrophages and contributes to fine control of innate immunity in lungs
Growing evidence suggests that versican is important in the innate immune response to lung infection. Our goal was to understand the regulation of macrophage-derived versican and the role it plays in innate immunity. We first defined the signaling events that regulate versican expression, using bone marrow-derived macrophages (BMDMs) from mice lacking specific Toll-like receptors (TLRs), TLR adaptor molecules, or the type I interferon receptor (IFNAR1). We show that LPS and polyinosinic-polycytidylic acid [poly(I:C)] trigger a signaling cascade involving TLR3 or TLR4, the Trif adaptor, type I interferons, and IFNAR1, leadi...
Source: AJP: Lung Cellular and Molecular Physiology - December 1, 2017 Category: Respiratory Medicine Authors: Chang, M. Y., Kang, I., Gale, M., Manicone, A. M., Kinsella, M. G., Braun, K. R., Wigmosta, T., Parks, W. C., Altemeier, W. A., Wight, T. N., Frevert, C. W. Tags: RESEARCH ARTICLE Source Type: research

Pollen-induced oxidative DNA damage response regulates miRNAs controlling allergic inflammation
A mucosal oxidative burst is a hallmark response to pollen exposure that promotes allergic inflammatory responses. Reactive species constituents of oxidative stress signal via the modification of cellular molecules including nucleic acids. One of the most abundant forms of oxidative genomic base damage is 8-oxo-7,8-dihydroguanine (8-oxoG), which is removed from DNA by 8-oxoguanine DNA glycosylase 1 (OGG1). OGG1 in complex with 8-oxoG acts as a GDP-GTP exchange factor and induces acute inflammation; however, the mechanism(s) by which OGG1 signaling regulates allergic airway inflammation is not known. Here, we postulate that...
Source: AJP: Lung Cellular and Molecular Physiology - December 1, 2017 Category: Respiratory Medicine Authors: Aguilera-Aguirre, L., Hao, W., Pan, L., Li, X., Saavedra-Molina, A., Bacsi, A., Radak, Z., Sur, S., Brasier, A. R., Ba, X., Boldogh, I. Tags: RESEARCH ARTICLE Source Type: research

Alcohol abuse is associated with enhanced pulmonary and systemic xanthine oxidoreductase activity
Acute respiratory distress syndrome (ARDS) is a common and devastating disorder. Alcohol use disorders (AUDs) increase ARDS risk and worsen outcomes through mechanisms that may include enhancement of pulmonary oxidative stress. Alcohol consumption increases activity of the enzyme xanthine oxidoreductase (XOR) that contributes to production of both reactive oxygen species (ROS) and uric acid, a damage-associated molecular pattern. These by-products have the potential to modulate proinflammatory pathways, such as those involving cyclooxygenase (COX)-2, and to activate the nucleotide-binding domain, leucine-rich-containing fa...
Source: AJP: Lung Cellular and Molecular Physiology - December 1, 2017 Category: Respiratory Medicine Authors: Fini, M. A., Gaydos, J., McNally, A., Karoor, V., Burnham, E. L. Tags: RESEARCH ARTICLE Source Type: research

Hyperoxia treatment of TREK-1/TREK-2/TRAAK-deficient mice is associated with a reduction in surfactant proteins
We previously proposed a role for the two-pore domain potassium (K2P) channel TREK-1 in hyperoxia (HO)-induced lung injury. To determine whether redundancy among the three TREK isoforms (TREK-1, TREK-2, and TRAAK) could protect from HO-induced injury, we now examined the effect of deletion of all three TREK isoforms in a clinically relevant scenario of prolonged HO exposure and mechanical ventilation (MV). We exposed WT and TREK-1/TREK-2/TRAAK-deficient [triple knockout (KO)] mice to either room air, 72-h HO, MV [high and low tidal volume (TV)], or a combination of HO + MV and measured quasistatic lung compliance, bronchoa...
Source: AJP: Lung Cellular and Molecular Physiology - December 1, 2017 Category: Respiratory Medicine Authors: Schwingshackl, A., Lopez, B., Teng, B., Luellen, C., Lesage, F., Belperio, J., Olcese, R., Waters, C. M. Tags: RESEARCH ARTICLE Source Type: research

Platelet CLEC-2 protects against lung injury via effects of its ligand podoplanin on inflammatory alveolar macrophages in the mouse
There is no therapeutic intervention proven to prevent acute respiratory distress syndrome (ARDS). Novel mechanistic insights into the pathophysiology of ARDS are therefore required. Platelets are implicated in regulating many of the pathogenic processes that occur during ARDS; however, the mechanisms remain elusive. The platelet receptor CLEC-2 has been shown to regulate vascular integrity at sites of acute inflammation. Therefore the purpose of this study was to establish the role of CLEC-2 and its ligand podoplanin in a mouse model of ARDS. Platelet-specific CLEC-2-deficient, as well as alveolar epithelial type I cell (...
Source: AJP: Lung Cellular and Molecular Physiology - December 1, 2017 Category: Respiratory Medicine Authors: Lax, S., Rayes, J., Wichaiyo, S., Haining, E. J., Lowe, K., Grygielska, B., Laloo, R., Flodby, P., Borok, Z., Crandall, E. D., Thickett, D. R., Watson, S. P. Tags: RESEARCH ARTICLE Source Type: research

Blockade of extracellular heat shock protein 90{alpha} by 1G6-D7 attenuates pulmonary fibrosis through inhibiting ERK signaling
In conclusion, 1G6-D7 significantly protects against BLM-induced pulmonary fibrosis by ameliorating fibroblast activation and ECM production, which may be through blocking ERK signaling. Our results suggest a safer molecular therapy, 1G6-D7, in pulmonary fibrosis. (Source: AJP: Lung Cellular and Molecular Physiology)
Source: AJP: Lung Cellular and Molecular Physiology - December 1, 2017 Category: Respiratory Medicine Authors: Dong, H., Luo, L., Zou, M., Huang, C., Wan, X., Hu, Y., Le, Y., Zhao, H., Li, W., Zou, F., Cai, S. Tags: RESEARCH ARTICLE Source Type: research

Sexual dimorphism of the pulmonary transcriptome in neonatal hyperoxic lung injury: identification of angiogenesis as a key pathway
In conclusion, we provide novel molecular insights into differential sex-specific modulation of the pulmonary transcriptome in neonatal hyperoxic lung injury and highlight angiogenesis as one of the crucial differentially modulated pathways. (Source: AJP: Lung Cellular and Molecular Physiology)
Source: AJP: Lung Cellular and Molecular Physiology - December 1, 2017 Category: Respiratory Medicine Authors: Coarfa, C., Zhang, Y., Maity, S., Perera, D. N., Jiang, W., Wang, L., Couroucli, X., Moorthy, B., Lingappan, K. Tags: RESEARCH ARTICLE Source Type: research

Invariant natural killer T cells promote immunogenic maturation of lung dendritic cells in mouse models of asthma
Our previous study showed that invariant natural killer T (iNKT) cells might act as an adjuvant to promote Th2 inflammatory responses in an OVA-induced mouse model of allergic asthma, but the mechanism remains unknown. To clarify the underlying mechanism through which iNKT cells promote Th2 inflammatory responses, we investigated the modulatory influence of iNKT cells on phenotypic and functional maturation of lung dendritic cells (LDCs) using iNKT cell-knockout mice, specific iNKT cell activation, coculture experiments, and adoptive transfer of iNKT cells in mouse models of asthma. Our data showed that iNKT cell deficienc...
Source: AJP: Lung Cellular and Molecular Physiology - December 1, 2017 Category: Respiratory Medicine Authors: He, Q., Liu, L., Yang, Q., Wang, A., Chen, S., Li, R., Huang, Y., Zhang, G., Ding, X., Yu, H., Hu, S., Nie, H. Tags: RESEARCH ARTICLE Source Type: research

Reply to "Letter to the Editor: The effects of electronic cigarette aerosol exposure on inflammation and lung function in mice"
(Source: AJP: Lung Cellular and Molecular Physiology)
Source: AJP: Lung Cellular and Molecular Physiology - November 6, 2017 Category: Respiratory Medicine Authors: Larcombe, A. N., Janka, M. A., Mullins, B. J., Berry, L. J., Bredin, A., Franklin, P. J. Tags: LETTER TO THE EDITOR Source Type: research