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: Farsalinos, K., Kistler, K. A., Gillman, G. Tags: LETTER TO THE EDITOR Source Type: research

Reply to "Letter to the Editor: Pulmonary toxicity of electronic cigarettes: more doubts than certainties"
(Source: AJP: Lung Cellular and Molecular Physiology)
Source: AJP: Lung Cellular and Molecular Physiology - November 6, 2017 Category: Respiratory Medicine Authors: Chun, L. F., Moazed, F., Calfee, C. S., Matthay, M. A., Gotts, J. E. Tags: LETTER TO THE EDITOR Source Type: research

Letter to the Editor: Pulmonary toxicity of electronic cigarettes: more doubts than certainties
(Source: AJP: Lung Cellular and Molecular Physiology)
Source: AJP: Lung Cellular and Molecular Physiology - November 6, 2017 Category: Respiratory Medicine Authors: Caruso, M., Mendelsohn, C. P., Polosa, R. Tags: LETTER TO THE EDITOR Source Type: research

Preserved right ventricular integrity in a new telemetric rat model of severe pulmonary hypertension
We describe here a novel telemetry catheter implantation technique, where the device is advanced into the pulmonary artery via the remaining stump and the transmitter is placed in a subcutaneous pocket. A total of 105 rats were operated with a median (range) implantation time of 50 (30–88) min and an excellent perioperative survival of 93%. After monocrotaline induction on day 7, animals developed severe PAH with mean ± SD pressures of 75.9 ± 18.6 (systolic), 55.0 ± 18.0 (mean), and 42.1 ± 21.3 mmHg (diastolic) after 4 wk. Postmortem, the animals showed severe right ventricular hypertrophy...
Source: AJP: Lung Cellular and Molecular Physiology - November 6, 2017 Category: Respiratory Medicine Authors: Schreiber, C., Eilenberg, M., Kiss, A., Bergmeister, H., Podesser, B., Mascherbauer, J., Bonderman, D. Tags: INNOVATIVE METHODOLOGY Source Type: research

Levosimendan prevents bronchoconstriction and adverse respiratory tissue mechanical changes in rabbits
Levosimendan has a calcium-sensitizing effect in the myocardium and opens ATP-sensitive potassium channels (KATP) in vascular smooth muscle. Because airway smooth muscle also expresses KATP, we characterized the protective potential of levosimendan against increased airway and respiratory tissue resistances. Animals were administered levosimendan alone (group L), levosimendan after pretreatment with a KATP channel blocker (glibenclamide, group LG), glibenclamide only (group G), or solvent alone (dextrose, group C). Airway resistance (Raw), tissue damping, and elastance were determined by forced oscillations under baseline ...
Source: AJP: Lung Cellular and Molecular Physiology - November 6, 2017 Category: Respiratory Medicine Authors: Babik, B., Balogh, A. L., Sudy, R., Ivankovitsne-Kiss, O., Fodor, G. H., Petak, F. Tags: RESEARCH ARTICLE Source Type: research

Oxygen-dependent changes in lung development do not affect epithelial infection with influenza A virus
Infants born prematurely often require supplemental oxygen, which contributes to aberrant lung development and increased pulmonary morbidity following a respiratory viral infection. We have been using a mouse model to understand how early-life hyperoxia affects the adult lung response to influenza A virus (IAV) infection. Prior studies showed how neonatal hyperoxia (100% oxygen) increased sensitivity of adult mice to infection with IAV [IAV (A/Hong Kong/X31) H3N2] as defined by persistent inflammation, pulmonary fibrosis, and mortality. Since neonatal hyperoxia alters lung structure, we used a novel fluorescence-expressing...
Source: AJP: Lung Cellular and Molecular Physiology - November 6, 2017 Category: Respiratory Medicine Authors: Domm, W., Yee, M., Misra, R. S., Gelein, R., Nogales, A., Martinez-Sobrido, L., OReilly, M. A. Tags: RESEARCH ARTICLE Source Type: research

Alternative pre-mRNA splicing of Toll-like receptor signaling components in peripheral blood mononuclear cells from patients with ARDS
A key physiological feature of acute respiratory distress syndrome (ARDS) is inflammation. Toll-like receptor (TLR) signaling is required to combat the infection that underlies many ARDS cases but also contributes to pathological inflammation. Several TLR signaling pathway genes encoding positive effectors of inflammation also produce alternatively spliced mRNAs encoding negative regulators of inflammation. An imbalance between these isoforms could contribute to pathological inflammation and disease severity. To determine whether splicing in TLR pathways is altered in patients with ARDS, we monitored alternative splicing o...
Source: AJP: Lung Cellular and Molecular Physiology - November 6, 2017 Category: Respiratory Medicine Authors: Blumhagen, R. Z., Hedin, B. R., Malcolm, K. C., Burnham, E. L., Moss, M., Abraham, E., Huie, T. J., Nick, J. A., Fingerlin, T. E., Alper, S. Tags: RESEARCH ARTICLE Source Type: research

CYP2E1 regulates the development of radiation-induced pulmonary fibrosis via ER stress- and ROS-dependent mechanisms
This study was conducted to identify the molecular mechanism responsible for RIPF. We revealed that the transcriptional level of cytochrome P450 2E1 (CYP2E1) was elevated by examining expression profile analysis of RIPF mouse models. We also confirmed that CYP2E1 regulated levels of endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) in alveolar epithelial type II (AE2) cells and lung fibroblasts. Inhibition of CYP2E1 via its siRNA or inhibitor significantly attenuated epithelial-to-mesenchymal transition and apoptosis of AE2 cells, as well as myofibroblast formation induced by radiation. Finally, the effec...
Source: AJP: Lung Cellular and Molecular Physiology - November 6, 2017 Category: Respiratory Medicine Authors: Son, B., Kwon, T., Lee, S., Han, I., Kim, W., Youn, H., Youn, B. Tags: RESEARCH ARTICLE Source Type: research

Endothelial cell-related autophagic pathways in Sugen/hypoxia-exposed pulmonary arterial hypertensive rats
This study investigated the time-dependent role of the autophagic pathway in pulmonary vascular ECs and pulmonary vascular EC kinesis in a severe PAH rat model (Sugen/hypoxia rat) and evaluated whether timely induction of the autophagic pathway by rapamycin improves PAH. Hemodynamic and histological examinations as well as flow cytometry of pulmonary vascular EC-related autophagic pathways and pulmonary vascular EC kinetics in lung cell suspensions were performed. The time-dependent and therapeutic effects of rapamycin on the autophagic pathway were also assessed. Sugen/hypoxia rats treated with the vascular endothelial gr...
Source: AJP: Lung Cellular and Molecular Physiology - November 6, 2017 Category: Respiratory Medicine Authors: Kato, F., Sakao, S., Takeuchi, T., Suzuki, T., Nishimura, R., Yasuda, T., Tanabe, N., Tatsumi, K. Tags: RESEARCH ARTICLE Source Type: research

Aquaporin 1-mediated changes in pulmonary arterial smooth muscle cell migration and proliferation involve {beta}-catenin
Exposure to hypoxia induces migration and proliferation of pulmonary arterial smooth muscle cells (PASMCs), leading to vascular remodeling and contributing to the development of hypoxic pulmonary hypertension. The mechanisms controlling PASMC growth and motility are incompletely understood, although aquaporin 1 (AQP1) plays an important role. In tumor, kidney, and stem cells, AQP1 has been shown to interact with β-catenin, a dual function protein that activates the transcription of crucial target genes (i.e., c-Myc and cyclin D1) related to cell migration and proliferation. Thus the goal of this study was to examine m...
Source: AJP: Lung Cellular and Molecular Physiology - November 6, 2017 Category: Respiratory Medicine Authors: Yun, X., Jiang, H., Lai, N., Wang, J., Shimoda, L. A. Tags: RESEARCH ARTICLE Source Type: research

Fra-2 negatively regulates postnatal alveolar septation by modulating myofibroblast function
Mice that globally overexpress the transcription factor Fos-related antigen-2 (Fra-2) develop extensive pulmonary fibrosis and pulmonary vascular remodeling. To determine if these phenotypes are a consequence of ectopic Fra-2 expression in vascular smooth muscle cells and myofibroblasts, we generated mice that overexpress Fra-2 specifically in these cell types (α-SMA-rtTA;tetO-Fra-2). Surprisingly, these mice did not develop vascular remodeling or pulmonary fibrosis but did develop a spontaneous emphysema-like phenotype characterized by alveolar enlargement. Secondary septa formation is an important step in the norma...
Source: AJP: Lung Cellular and Molecular Physiology - November 6, 2017 Category: Respiratory Medicine Authors: Tsujino, K., Li, J. T., Tsukui, T., Ren, X., Bakiri, L., Wagner, E., Sheppard, D. Tags: RESEARCH ARTICLE Source Type: research

Use of proper statistical techniques for research studies with small samples
In this review I discuss the appropriateness of various statistical methods for use with small sample sizes. I review the assumptions and limitations of these methods and provide recommendations for figures and statistical tests. (Source: AJP: Lung Cellular and Molecular Physiology)
Source: AJP: Lung Cellular and Molecular Physiology - November 6, 2017 Category: Respiratory Medicine Authors: Morgan, C. J. Tags: REVIEW Source Type: research

Ion channels of the lung and their role in disease pathogenesis
Maintenance of normal epithelial ion and water transport in the lungs includes providing a thin layer of surface liquid that coats the conducting airways. This airway surface liquid is critical for normal lung function in a number of ways but, perhaps most importantly, is required for normal mucociliary clearance and bacterial removal. Preservation of the appropriate level of hydration, pH, and viscosity for the airway surface liquid requires the proper regulation and function of a battery of different types of ion channels and transporters. Here we discuss how alterations in ion channel/transporter function often lead to ...
Source: AJP: Lung Cellular and Molecular Physiology - November 6, 2017 Category: Respiratory Medicine Authors: Bartoszewski, R., Matalon, S., Collawn, J. F. Tags: REVIEW Source Type: research

Influenza virus infection alters ion channel function of airway and alveolar cells: mechanisms and physiological sequelae
The cystic fibrosis transmembrane conductance regulator (CFTR) and the amiloride-sensitive epithelial sodium channels (ENaC) are located in the apical membranes of airway and alveolar epithelial cells. These transporters play an important role in the regulation of lung fluid balance across airway and alveolar epithelia by being the conduits for chloride (Cl–) and bicarbonate (HCO3–) secretion and sodium (Na+) ion absorption, respectively. The functional role of these channels in the respiratory tract is to maintain the optimum volume and ionic composition of the bronchial periciliary fluid (PCL) and alveolar li...
Source: AJP: Lung Cellular and Molecular Physiology - November 6, 2017 Category: Respiratory Medicine Authors: Londino, J. D., Lazrak, A., Collawn, J. F., Bebok, Z., Harrod, K. S., Matalon, S. Tags: REVIEW Source Type: research

Metabolic characterization and RNA profiling reveal glycolytic dependence of profibrotic phenotype of alveolar macrophages in lung fibrosis
In this study, we comprehensively analyzed the expression profile and main metabolic programs in alveolar macrophages from mice with or without experimental pulmonary fibrosis. We found that alveolar macrophages from both bleomycin and active TGF-β1-induced fibrotic mouse lungs demonstrated a primarily profibrotic M2-like profile that was distinct from the well-defined M1 or any of the M2 subtypes. More importantly, we found that fibrotic lung alveolar macrophages assumed augmented glycolysis, which was likely attributed to enhanced expression of multiple key glycolytic mediators. We also found that fatty acid oxidati...
Source: AJP: Lung Cellular and Molecular Physiology - November 1, 2017 Category: Respiratory Medicine Authors: Xie, N., Cui, H., Ge, J., Banerjee, S., Guo, S., Dubey, S., Abraham, E., Liu, R.-M., Liu, G. Tags: RESEARCH ARTICLE Source Type: research