Cooperative signaling by TGF-{beta}1 and WNT-11 drives sm-{alpha}-actin expression in smooth muscle via Rho kinase-actin-MRTF-A signaling
Airway smooth muscle (ASM) remodeling is a key feature in asthma and includes changes in smooth muscle-specific gene and protein expression. Despite this being a major contributor to asthma pathobiology, our understanding of the mechanisms governing ASM remodeling remains poor. Here, we studied the functional interaction between WNT-11 and TGF-β1 in ASM cells. We demonstrate that WNT-11 is preferentially expressed in contractile myocytes and is strongly upregulated following TGF-β1-induced myocyte maturation. Knock-down of WNT-11 attenuated TGF-β1-induced smooth muscle (sm)-α-actin expression in ASM ce...
Source: AJP: Lung Cellular and Molecular Physiology - August 31, 2016 Category: Respiratory Medicine Authors: Kumawat, K., Koopmans, T., Menzen, M. H., Prins, A., Smit, M., Halayko, A. J., Gosens, R. Tags: CALL FOR PAPERS Source Type: research

Corrigendum
(Source: AJP: Lung Cellular and Molecular Physiology)
Source: AJP: Lung Cellular and Molecular Physiology - August 8, 2016 Category: Respiratory Medicine Tags: CORRIGENDA Source Type: research

Response to comments by Emma et al.
(Source: AJP: Lung Cellular and Molecular Physiology)
Source: AJP: Lung Cellular and Molecular Physiology - August 8, 2016 Category: Respiratory Medicine Authors: Jaspers, I. Tags: LETTERS TO THE EDITOR Source Type: research

Smoking history can influence the epigenetic and gene expression profile
(Source: AJP: Lung Cellular and Molecular Physiology)
Source: AJP: Lung Cellular and Molecular Physiology - August 8, 2016 Category: Respiratory Medicine Authors: Emma, R., Caruso, M., Polosa, R. Tags: LETTERS TO THE EDITOR Source Type: research

Phospholipase C-{varepsilon} signaling mediates endothelial cell inflammation and barrier disruption in acute lung injury
Phospholipase C- (PLC-) is a unique PLC isoform that can be regulated by multiple signaling inputs from both Ras family GTPases and heterotrimeric G proteins and has primary sites of expression in the heart and lung. Whereas the role of PLC- in cardiac function and pathology has been documented, its relevance in acute lung injury (ALI) is unclear. We used PLC-–/– mice to address the role of PLC- in regulating lung vascular inflammation and injury in an aerosolized bacterial LPS inhalation mouse model of ALI. PLC-–/– mice showed a marked decrease in LPS-induced proinflammatory mediators (ICAM-1, VCAM...
Source: AJP: Lung Cellular and Molecular Physiology - August 8, 2016 Category: Respiratory Medicine Authors: Bijli, K. M., Fazal, F., Slavin, S. A., Leonard, A., Grose, V., Alexander, W. B., Smrcka, A. V., Rahman, A. Tags: ARTICLES Source Type: research

Granzyme A impairs host defense during Streptococcus pneumoniae pneumonia
Streptococcus pneumoniae is the most common causative pathogen in community-acquired pneumonia (CAP). Granzyme A (GzmA) is a serine protease produced by a variety of cell types involved in the immune response. We sought to determine the role of GzmA on the host response during pneumococcal pneumonia. GzmA was measured in bronchoalveolar lavage fluid (BALF) harvested from CAP patients from the infected and contralateral uninfected side and in lung tissue slides from CAP patients and controls. In CAP patients, GzmA levels were increased in BALF obtained from the infected lung. Human lungs showed constitutive GzmA expression ...
Source: AJP: Lung Cellular and Molecular Physiology - August 8, 2016 Category: Respiratory Medicine Authors: van den Boogaard, F. E., van Gisbergen, K. P. J. M., Vernooy, J. H., Medema, J. P., Roelofs, J. J. T. H., van Zoelen, M. A. D., Endeman, H., Biesma, D. H., Boon, L., van't Veer, C., de Vos, A. F., van der Poll, T. Tags: CALL FOR PAPERS Source Type: research

Macrophage micro-RNA-155 promotes lipopolysaccharide-induced acute lung injury in mice and rats
Micro-RNA (miR)-155 is a novel gene regulator with important roles in inflammation. Herein, our study aimed to explore the role of miR-155 in LPS-induced acute lung injury(ALI). ALI in mice was induced by intratracheally delivered LPS. Loss-of-function experiments performed on miR-155 knockout mice showed that miR-155 gene inactivation protected mice from LPS-induced ALI, as manifested by preserved lung permeability and reduced lung inflammation compared with wild-type controls. Bone marrow transplantation experiments identified leukocytes, but not lung parenchymal-derived miR-155-promoted acute lung inflammation. Real-tim...
Source: AJP: Lung Cellular and Molecular Physiology - August 8, 2016 Category: Respiratory Medicine Authors: Wang, W., Liu, Z., Su, J., Chen, W.-S., Wang, X.-W., Bai, S.-X., Zhang, J.-Z., Yu, S.-Q. Tags: CALL FOR PAPERS Source Type: research

Sex-specific differences in neonatal hyperoxic lung injury
Male sex is considered an independent predictor for the development of bronchopulmonary dysplasia (BPD) after adjusting for other confounders. BPD is characterized by an arrest in lung development with marked impairment of alveolar septation and vascular development. The reasons underlying sexually dimorphic outcomes in premature neonates are not known. In this investigation, we tested the hypothesis that male neonatal mice will be more susceptible to hyperoxic lung injury and will display larger arrest in lung alveolarization. Neonatal male and female mice (C57BL/6) were exposed to hyperoxia [95% FiO2, postnatal day (PND)...
Source: AJP: Lung Cellular and Molecular Physiology - August 8, 2016 Category: Respiratory Medicine Authors: Lingappan, K., Jiang, W., Wang, L., Moorthy, B. Tags: CALL FOR PAPERS Source Type: research

Tumor necrosis factor regulates NMDA receptor-mediated airway smooth muscle contractile function and airway responsiveness
We have shown that N-methyl-d-aspartate receptors (NMDA-Rs) are receptor-operated calcium entry channels in human airway smooth muscle (HASM) during contraction. Tumor necrosis factor (TNF) augments smooth muscle contractility by influencing pathways that regulate intracellular calcium flux and can alter NMDA-R expression and activity in cortical neurons and glial cells. We hypothesized that NMDA-R-mediated Ca2+ and contractile responses of ASM can be altered by inflammatory mediators, including TNF. In cultured HASM cells, we assessed TNF (10 ng/ml, 48 h) effect on NMDA-R subunit abundance by quantitative PCR, confocal im...
Source: AJP: Lung Cellular and Molecular Physiology - August 8, 2016 Category: Respiratory Medicine Authors: Anaparti, V., Pascoe, C. D., Jha, A., Mahood, T. H., Ilarraza, R., Unruh, H., Moqbel, R., Halayko, A. J. Tags: CALL FOR PAPERS Source Type: research

Using cultured endothelial cells to study endothelial barrier dysfunction: Challenges and opportunities
Despite considerable progress in the understanding of endothelial barrier regulation and the identification of approaches that have the potential to improve endothelial barrier function, no drug- or stem cell-based therapy is presently available to reverse the widespread vascular leak that is observed in acute respiratory distress syndrome (ARDS) and sepsis. The translational gap suggests a need to develop experimental approaches and tools that better mimic the complex environment of the microcirculation in which the vascular leak develops. Recent studies have identified several elements of this microenvironment. Among the...
Source: AJP: Lung Cellular and Molecular Physiology - August 8, 2016 Category: Respiratory Medicine Authors: Aman, J., Weijers, E. M., van Nieuw Amerongen, G. P., Malik, A. B., van Hinsbergh, V. W. M. Tags: CALL FOR PAPERS Source Type: research

Differential regulation of autophagy and mitophagy in pulmonary diseases
Lysosomal-mediated degradation of intracellular lipids, proteins and organelles, known as autophagy, represents a inducible adaptive response to lung injury resulting from exposure to insults, such as hypoxia, microbes, inflammation, ischemia-reperfusion, pharmaceuticals (e.g., bleomycin), or inhaled xenobiotics (i.e., air pollution, cigarette smoke). This process clears damaged or toxic cellular constituents and facilitates cell survival in stressful environments. Autophagic degradation of dysfunctional or damaged mitochondria is termed mitophagy. Enhanced mitophagy is usually an early response to promote survival. Howeve...
Source: AJP: Lung Cellular and Molecular Physiology - August 8, 2016 Category: Respiratory Medicine Authors: Aggarwal, S., Mannam, P., Zhang, J. Tags: PERSPECTIVES Source Type: research

Glucocorticoid and TNF signaling converge at A20 (TNFAIP3) to repress airway smooth muscle cytokine expression
Airway smooth muscle is a major target tissue for glucocorticoid (GC)-based asthma therapies, however, molecular mechanisms through which the GC receptor (GR) exerts therapeutic effects in this key airway cell type have not been fully elucidated. We previously identified the nuclear factor-B (NF-B) inhibitor, A20 (TNFAIP3), as a mediator of cytokine repression by glucocorticoids (GCs) in airway epithelial cells and defined cooperative regulation of anti-inflammatory genes by GR and NF-B as a key mechanistic underpinning of airway epithelial GR function. Here, we expand on these findings to determine whether a similar mecha...
Source: AJP: Lung Cellular and Molecular Physiology - July 31, 2016 Category: Respiratory Medicine Authors: Sasse, S. K., Altonsy, M. O., Kadiyala, V., Cao, G., Panettieri, R. A., Gerber, A. N. Tags: ARTICLES Source Type: research

Brief mechanical ventilation causes differential epithelial repair along the airways of fetal, preterm lambs
Mechanical ventilation of preterm lambs causes lung inflammation and injury to the airway epithelium, which is repaired by 15 days after ventilation. In mice, activated basal cells (p63+, KRT14+, KRT8+) initiate injury repair to the trachea, whereas club cells coordinate distal airway repair. In both human and sheep, basal cells line the pseudostratified airways to the distal bronchioles with club cells only present in terminal bronchioles. Mechanical ventilation causes airway epithelial injury that is repaired through basal cell activation in the fetal lung. Ewes at 123 ± 1 day gestational age had the head and ches...
Source: AJP: Lung Cellular and Molecular Physiology - July 31, 2016 Category: Respiratory Medicine Authors: Deptula, N., Royse, E., Kemp, M. W., Miura, Y., Kallapur, S. G., Jobe, A. H., Hillman, N. H. Tags: ARTICLES Source Type: research

MiR-196a regulates heme oxygenase-1 by silencing Bach1 in the neonatal mouse lung
This report is the first to show developmental differences in lung miR-196a and its effect on Bach1 and HO-1 expression at baseline and in hyperoxia. (Source: AJP: Lung Cellular and Molecular Physiology)
Source: AJP: Lung Cellular and Molecular Physiology - July 31, 2016 Category: Respiratory Medicine Authors: Go, H., La, P., Namba, F., Ito, M., Yang, G., Brydun, A., Igarashi, K., Dennery, P. A. Tags: ARTICLES Source Type: research

Dose dependency of outcomes of intrapleural fibrinolytic therapy in new rabbit empyema models
The incidence of empyema (EMP) is increasing worldwide; EMP generally occurs with pleural loculation and impaired drainage is often treated with intrapleural fibrinolytic therapy (IPFT) or surgery. A number of IPFT options are used clinically with empiric dosing and variable outcomes in adults. To evaluate mechanisms governing intrapleural fibrinolysis and disease outcomes, models of Pasteurella multocida and Streptococcus pneumoniae were generated in rabbits and the animals were treated with either human tissue (tPA) plasminogen activator or prourokinase (scuPA). Rabbit EMP was characterized by the development of pleural ...
Source: AJP: Lung Cellular and Molecular Physiology - July 31, 2016 Category: Respiratory Medicine Authors: Komissarov, A. A., Florova, G., Azghani, A. O., Buchanan, A., Boren, J., Allen, T., Rahman, N. M., Koenig, K., Chamiso, M., Karandashova, S., Henry, J., Idell, S. Tags: ARTICLES Source Type: research