AJP: Lung Cellular and Molecular Physiology This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

Sirtuin 7 is decreased in pulmonary fibrosis and regulates the fibrotic phenotype of lung fibroblasts
In conclusion, the decline in SIRT7 in lung fibroblasts has a profibrotic effect, which is mediated by changes in Smad3 levels. (Source: AJP: Lung Cellular and Molecular Physiology)
Source: AJP: Lung Cellular and Molecular Physiology - June 5, 2017 Category: Respiratory Medicine Authors: Wyman, A. E., Noor, Z., Fishelevich, R., Lockatell, V., Shah, N. G., Todd, N. W., Atamas, S. P. Tags: RESEARCH ARTICLE Source Type: research

TGF-{beta}1 stimulates HDAC4 nucleus-to-cytoplasm translocation and NADPH oxidase 4-derived reactive oxygen species in normal human lung fibroblasts
Myofibroblasts are important mediators of fibrogenesis; thus blocking fibroblast-to-myofibroblast differentiation (FMD) may be an effective strategy to treat pulmonary fibrosis (PF). Previously, we reported that histone deacetylase 4 (HDAC4) activity is necessary for transforming growth factor-β1 (TGF-β1)-induced human lung FMD. Here, we show that TGF-β1 increases NADPH oxidase 4 (NOX4) mRNA and protein expression in normal human lung fibroblasts (NHLFs) and causes nuclear export of HDAC4. Application of the NOX family inhibitor diphenyleneiodonium chloride reduces TGF-β1-induced HDAC4 nuclear export, e...
Source: AJP: Lung Cellular and Molecular Physiology - June 5, 2017 Category: Respiratory Medicine Authors: Guo, W., Saito, S., Sanchez, C. G., Zhuang, Y., Gongora Rosero, R. E., Shan, B., Luo, F., Lasky, J. A. Tags: RESEARCH ARTICLE Source Type: research

Focal adhesion kinase signaling determines the fate of lung epithelial cells in response to TGF-{beta}
In this report, we explore the role of focal adhesion kinase (FAK) signaling in determining the fate of lung epithelial cells in response to transforming growth factor-β1 (TGF-β1). Rat type II alveolar epithelial cells (RLE-6TN) were treated with or without TGF-β1, and the expressions of mesenchymal markers, phenotype, and function were analyzed. Pharmacological protein kinase inhibitors were utilized to screen for SMAD-dependent and -independent pathways. SMAD and FAK signaling was analyzed using siRNA knockdown, inhibitors, and expression of a mutant construct of FAK. Apoptosis was measured using cleaved c...
Source: AJP: Lung Cellular and Molecular Physiology - June 5, 2017 Category: Respiratory Medicine Authors: Ding, Q., Subramanian, I., Luckhardt, T. R., Che, P., Waghray, M., Zhao, X.-K., Bone, N., Kurundkar, A. R., Hecker, L., Hu, M., Zhou, Y., Horowitz, J. C., Vittal, R., Thannickal, V. J. Tags: RESEARCH ARTICLE Source Type: research

The CFTR trafficking mutation F508del inhibits the constitutive activity of SLC26A9
We examined whether changes in SLC26A9 constitutive activity could be attributed to a loss of CFTR trafficking, and what role PDZ interactions played. HEK293 coexpressing SLC26A9 with the trafficking mutant F508del CFTR exhibited a significant reduction in constitutive current compared with cells coexpressing SLC26A9 and wt CFTR. We found that SLC26A9 exhibits complex glycosylation when coexpressed with F508del CFTR, but its expression at the plasma membrane is decreased. SLC26A9 interacted with both NHERF-1 and CAL, and its interaction with both significantly increased with coexpression of wt CFTR. However, coexpression w...
Source: AJP: Lung Cellular and Molecular Physiology - June 5, 2017 Category: Respiratory Medicine Authors: Bertrand, C. A., Mitra, S., Mishra, S. K., Wang, X., Zhao, Y., Pilewski, J. M., Madden, D. R., Frizzell, R. A. Tags: RESEARCH ARTICLE Source Type: research

Loss of lung WWOX expression causes neutrophilic inflammation
The tumor suppressor WW domain-containing oxidoreductase (WWOX) exhibits regulatory interactions with an array of transcription factors and signaling molecules that are positioned at the well-known crossroads between inflammation and cancer. WWOX is also subject to downregulation by genotoxic environmental exposures, making it of potential interest to the study of lung pathobiology. Knockdown of lung WWOX expression in mice was observed to cause neutrophil influx and was accompanied by a corresponding vascular leak and inflammatory cytokine production. In cultured human alveolar epithelial cells, loss of WWOX expression re...
Source: AJP: Lung Cellular and Molecular Physiology - June 5, 2017 Category: Respiratory Medicine Authors: Singla, S., Chen, J., Sethuraman, S., Sysol, J. R., Gampa, A., Zhao, S., Machado, R. F. Tags: RESEARCH ARTICLE Source Type: research

An ex vivo model to induce early fibrosis-like changes in human precision-cut lung slices
Idiopathic pulmonary fibrosis (IPF) is a devastating chronic interstitial lung disease (ILD) characterized by lung tissue scarring and high morbidity. Lung epithelial injury, myofibroblast activation, and deranged repair are believed to be key processes involved in disease onset and progression, but the exact molecular mechanisms behind IPF remain unclear. Several drugs have been shown to slow disease progression, but treatments that halt or reverse IPF progression have not been identified. Ex vivo models of human lung have been proposed for drug discovery, one of which is precision-cut lung slices (PCLS). Although PCLS pr...
Source: AJP: Lung Cellular and Molecular Physiology - June 1, 2017 Category: Respiratory Medicine Authors: Alsafadi, H. N., Staab-Weijnitz, C. A., Lehmann, M., Lindner, M., Peschel, B., Königshoff, M., Wagner, D. E. Tags: RAPID REPORT Source Type: research

Stereological monitoring of mouse lung alveolarization from the early postnatal period to adulthood
Postnatal lung maturation generates a large number of small alveoli, with concomitant thinning of alveolar septal walls, generating a large gas exchange surface area but minimizing the distance traversed by the gases. This demand for a large and thin gas exchange surface area is not met in disorders of lung development, such as bronchopulmonary dysplasia (BPD) histopathologically characterized by fewer, larger alveoli and thickened alveolar septal walls. Diseases such as BPD are often modeled in the laboratory mouse to better understand disease pathogenesis or to develop new interventional approaches. To date, there have b...
Source: AJP: Lung Cellular and Molecular Physiology - June 1, 2017 Category: Respiratory Medicine Authors: Pozarska, A., Rodriguez-Castillo, J. A., Surate Solaligue, D. E., Ntokou, A., Rath, P., Mizikova, I., Madurga, A., Mayer, K., Vadasz, I., Herold, S., Ahlbrecht, K., Seeger, W., Morty, R. E. Tags: RESEARCH ARTICLE Source Type: research

Airway smooth muscle dysfunction in Pompe (Gaa-/-) mice
Pompe disease is an autosomal recessive disorder caused by a deficiency of acid α-glucosidase (GAA), an enzyme responsible for hydrolyzing lysosomal glycogen. Deficiency of GAA leads to systemic glycogen accumulation in the lysosomes of skeletal muscle, motor neurons, and smooth muscle. Skeletal muscle and motor neuron pathology are known to contribute to respiratory insufficiency in Pompe disease, but the role of airway pathology has not been evaluated. Here we propose that GAA enzyme deficiency disrupts the function of the trachea and bronchi and this lower airway pathology contributes to respiratory insufficiency ...
Source: AJP: Lung Cellular and Molecular Physiology - June 1, 2017 Category: Respiratory Medicine Authors: Keeler, A. M., Liu, D., Zieger, M., Xiong, L., Salemi, J., Bellve, K., Byrne, B. J., Fuller, D. D., ZhuGe, R., ElMallah, M. K. Tags: RESEARCH ARTICLE Source Type: research

The innate immune response in fetal lung mesenchymal cells targets VEGFR2 expression and activity
In preterm infants, soluble inflammatory mediators target lung mesenchymal cells, disrupting airway and alveolar morphogenesis. However, how mesenchymal cells respond directly to microbial stimuli remains poorly characterized. Our objective was to measure the genome-wide innate immune response in fetal lung mesenchymal cells exposed to the bacterial endotoxin lipopolysaccharide (LPS). With the use of Affymetrix MoGene 1.0st arrays, we showed that LPS induced expression of unique innate immune transcripts heavily weighted toward CC and CXC family chemokines. The transcriptional response was different between cells from E11,...
Source: AJP: Lung Cellular and Molecular Physiology - June 1, 2017 Category: Respiratory Medicine Authors: Medal, R. M., Im, A. M., Yamamoto, Y., Lakhdari, O., Blackwell, T. S., Hoffman, H. M., Sahoo, D., Prince, L. S. Tags: RESEARCH ARTICLE Source Type: research

The circadian protein BMAL1 in myeloid cells is a negative regulator of allergic asthma
Our body clock drives rhythms in the expression of genes that have a 24-h periodicity. The transcription factor BMAL1 is a crucial component of the molecular clock. A number of physiological processes, including immune function, are modulated by the circadian clock. Asthma, a disease with very strong clinical evidence demonstrating regulation by circadian variation, is of particular relevance to circadian control of immunity. Airway hypersensitivity and asthma attacks are more common at night in humans. The molecular basis for this is unknown, and there is no model of asthma in animals with genetic distortion of the molecu...
Source: AJP: Lung Cellular and Molecular Physiology - June 1, 2017 Category: Respiratory Medicine Authors: Zasłona, Z., Case, S., Early, J. O., Lalor, S. J., McLoughlin, R. M., Curtis, A. M., ONeill, L. A. J. Tags: RESEARCH ARTICLE Source Type: research

Directional preference of airway smooth muscle mass increase in human asthmatic airways
Airway smooth muscle (ASM) orientation and morphology determine the ability of the muscle to constrict the airway. In asthma, ASM mass is increased, but it is unknown whether ASM orientation and morphology are altered as well or whether the remodeling at the source of the mass increase is ongoing. We dissected human airway trees from asthmatic and control lungs. Stained, intact airway sections were imaged in axial projection to show ASM bundle orientation, whereas cross-sectional histological slides were used to assess ASM area, bundle thickness, and ASM bundle-to-basement membrane distance. We also used these slides to as...
Source: AJP: Lung Cellular and Molecular Physiology - June 1, 2017 Category: Respiratory Medicine Authors: Ijpma, G., Panariti, A., Lauzon, A.-M., Martin, J. G. Tags: RESEARCH ARTICLE Source Type: research

{omega}-3 Polyunsaturated fatty acids accelerate airway repair by activating FFA4 in club cells
A G protein-coupled receptor (GPCR) named free fatty acid receptor 4 (FFA4, also known as GPR120) was found to act as a GPCR for -3 polyunsaturated fatty acids. Its expression has been reported in lung epithelial club cells. We investigated whether supplementation of the -3 fatty acids benefits lung health. Omacor (7.75 mg/kg), clinically prescribed preparation of -3 fatty acids, and FFA4-knockout mice were utilized in a naphthalene-induced mouse model of acute airway injury (1 injection of 30 mg/kg ip). Naphthalene injection induced complete destruction of bronchiolar epithelial cells within a day. Appearance of bronchiol...
Source: AJP: Lung Cellular and Molecular Physiology - June 1, 2017 Category: Respiratory Medicine Authors: Lee, K.-P., Park, S.-J., Kang, S., Koh, J.-M., Sato, K., Chung, H.-Y., Okajima, F., Im, D.-S. Tags: RESEARCH ARTICLE Source Type: research

PKC-dependent regulation of Kv7.5 channels by the bronchoconstrictor histamine in human airway smooth muscle cells
Kv7 potassium channels have recently been found to be expressed and functionally important for relaxation of airway smooth muscle. Previous research suggests that native Kv7 currents are inhibited following treatment of freshly isolated airway smooth muscle cells with bronchoconstrictor agonists, and in intact airways inhibition of Kv7 channels is sufficient to induce bronchiolar constriction. However, the mechanism by which Kv7 currents are inhibited by bronchoconstrictor agonists has yet to be elucidated. In the present study, native Kv7 currents in cultured human trachealis smooth muscle cells (HTSMCs) were observed to ...
Source: AJP: Lung Cellular and Molecular Physiology - June 1, 2017 Category: Respiratory Medicine Authors: Haick, J. M., Brueggemann, L. I., Cribbs, L. L., Denning, M. F., Schwartz, J., Byron, K. L. Tags: RESEARCH ARTICLE Source Type: research

Role of transient receptor potential vanilloid 1 in the modulation of airway smooth muscle tone and calcium handling
Asthma is a common disorder characterized, in part, by airway smooth muscle (ASM) hyperresponsiveness. Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel expressed on airway nerve fibers that modulates afferent signals, resulting in cough, and potentially bronchoconstriction. In the present study, the TRPV1 transcript was detected by RT-PCR in primary cultured human ASM cells, and the TRPV1 protein was detected in ASM of human trachea by immunohistochemistry. Proximity ligation assays suggest that TRPV1 is expressed in the sarcoplasmic reticulum membrane of human ASM cells in close associatio...
Source: AJP: Lung Cellular and Molecular Physiology - June 1, 2017 Category: Respiratory Medicine Authors: Yocum, G. T., Chen, J., Choi, C. H., Townsend, E. A., Zhang, Y., Xu, D., Fu, X. W., Sanderson, M. J., Emala, C. W. Tags: RESEARCH ARTICLE Source Type: research

Alveolar nonselective channels are ASIC1a/{alpha}-ENaC channels and contribute to AFC
A thin fluid layer in alveoli is normal and results from a balance of fluid entry and fluid uptake by transepithelial salt and water reabsorption. Conventional wisdom suggests the reabsorption is via epithelial Na+ channels (ENaC), but if all Na+ reabsorption were via ENaC, then amiloride, an ENaC inhibitor, should block alveolar fluid clearance (AFC). However, amiloride blocks only half of AFC. The reason for failure to block is clear from single-channel measurements from alveolar epithelial cells: ENaC channels are observed, but another channel is present at the same frequency that is nonselective for Na+ over K+, has a ...
Source: AJP: Lung Cellular and Molecular Physiology - June 1, 2017 Category: Respiratory Medicine Authors: Trac, P. T., Thai, T. L., Linck, V., Zou, L., Greenlee, M., Yue, Q., Al-Khalili, O., Alli, A. A., Eaton, A. F., Eaton, D. C. Tags: RESEARCH ARTICLE Source Type: research