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    4746 results match your criteria American Journal of Physiology - Lung Cellular and Molecular Physiology[Journal]

    1 OF 95

    Distinct niches within the extracellular matrix dictate fibroblast function in (cell-free) 3D lung tissue cultures.
    Am J Physiol Lung Cell Mol Physiol 2018 Jan 18. Epub 2018 Jan 18.
    Division of Respiratory Sciences and Critical Care Medicine, University of Colorado, United States.
    Instructive cues from the extracellular matrix (ECM) and their functional interplay with cells play pivotal roles for development, tissue repair, and disease. However, the precise nature of this interplay remains elusive. We used an innovative 3D cell culture ECM model by decellularizing ex vivo lung tissue scaffolds (d3D-LTCs) derived from diseased and healthy mouse lungs, which widely mimics the native (patho)physiological in vivo microenvironment. Read More

    Pulmonary vascular dysfunction secondary to pulmonary arterial hypertension: Insights gained through retrograde perfusion.
    Am J Physiol Lung Cell Mol Physiol 2018 Jan 18. Epub 2018 Jan 18.
    Physiology and Cell Biology and Medicine, Center for Lung Biology, University of South Alabama, United States.
    Here, we tested the hypothesis that severe pulmonary arterial hypertension impairs retrograde perfusion. To test this hypothesis, pulmonary arterial hypertension was induced in Fischer rats using a single injection of Sugen 5416 followed by 3 weeks of exposure to 10% hypoxia and then 2 weeks of normoxia. This Sugen 5416 and hypoxia regimen caused severe pulmonary arterial hypertension, with a Fulton Index of 0. Read More

    Fibrin Turnover and Organization of Pleural Injury: Bench to Bedside.
    Am J Physiol Lung Cell Mol Physiol 2018 Jan 18. Epub 2018 Jan 18.
    Biomedical Research, The University of Texas Health Center at Tyler, United States.
    Recent studies have shed new light on the role of the fibrinolytic system in the pathogenesis of pleural organization, including mechanisms by which the system regulates mesenchymal transition of mesothelial cells and how that process affects outcomes of pleural injury. The key contribution of plasminogen activator inhibitor-1 to the outcomes of pleural injury is now better understood as is its role in the regulation of intrapleural fibrinolytic therapy. In addition, mechanisms by which fibrinolysins are processed after intrapleural administration have now been elucidated, informing new candidate diagnostics and therapeutics for pleural loculation and failed drainage. Read More

    Neonatal hyperoxia depletes pulmonary vein cardiomyocytes in adult mice via mitochondrial oxidation.
    Am J Physiol Lung Cell Mol Physiol 2018 Jan 18. Epub 2018 Jan 18.
    Pediatrics, The University of Rochester, United States.
    Supplemental oxygen given to preterm infants has been associated with permanently altering postnatal lung development. Now that these individuals are reaching adulthood, there is growing concern that early-life oxygen exposure may also promote cardiovascular disease through poorly understood mechanisms. We previously reported that adult mice exposed to 100% oxygen between postnatal days 0-4 develop pulmonary hypertension defined pathologically by capillary rarefaction, dilation of arterioles and veins, cardiac failure, and a reduced lifespan. Read More

    Surfactant Protein C dampens inflammation by decreasing JAK/STAT activation during lung repair.
    Am J Physiol Lung Cell Mol Physiol 2018 Jan 18. Epub 2018 Jan 18.
    Yale University, United States.
    Surfactant Protein C (SPC), a key component of pulmonary surfactant, also plays a role in regulating inflammation. SPC deficiency in patients and mouse models is associated with increased inflammation and delayed repair, but the key drivers of SPC-regulated inflammation in response to injury are largely unknown. This study focuses on a new mechanism of SPC as an anti-inflammatory molecule using SPC-TK/SPC-KO (surfactant protein C-thymidine kinase/surfactant protein C knockout) mice, which represent a novel sterile injury model that mimics clinical acute respiratory distress syndrome (ARDS). Read More

    Mitochondrial dysfunction and pulmonary hypertension: Cause, Effect or Both.
    Am J Physiol Lung Cell Mol Physiol 2018 Jan 18. Epub 2018 Jan 18.
    Pulmonary and Critical Care, Yale University School of Medicine, United States.
    Pulmonary hypertension describes a heterogeneous disease defined by increased pulmonary artery pressures, and progressive increase in pulmonary vascular resistance due to pathologic remodeling of the pulmonary vasculature involving pulmonary endothelial cells, pericytes, and smooth muscle cells.  This process occurs under various conditions, and though these populations vary, the clinical manifestations are the same: progressive dyspnea, increases in right ventricular (RV) afterload and dysfunction, RV-pulmonary artery uncoupling, and right-sided heart failure with systemic circulatory collapse. The overall estimated 5-year survival rate is 72% in highly functioning patients, and as low as 28% for those presenting with advanced symptoms. Read More

    Transient stretch induces cytoskeletal fluidization through the severing action of cofilin.
    Am J Physiol Lung Cell Mol Physiol 2018 Jan 18. Epub 2018 Jan 18.
    Department of Environmental Health, Harvard School of Public Health, United States.
    With every deep inspiration (DI) or sigh the airway wall stretches, as do the airway smooth muscle cells that it contains. In response, the airway smooth muscle (ASM) cell undergoes rapid stretch-induced cytoskeletal fluidization. As a molecular mechanism underlying that ASM fluidization response, here we demonstrate a key role for the actin-severing protein, cofilin. Read More

    Serotonin 2A receptor inhibition protects against the development of pulmonary hypertension and pulmonary vascular remodeling in neonatal mice.
    Am J Physiol Lung Cell Mol Physiol 2018 Jan 18. Epub 2018 Jan 18.
    Pediatrics and Cardiovascular Pulmonary Research, University of Colorado Denver, United States.
    Pulmonary hypertension (PH) complicating bronchopulmonary dysplasia (BPD) worsens clinical outcomes in former preterm infants. Increased serotonin (5-hydroxytryptamine, 5-HT) signaling plays a prominent role in PH pathogenesis and progression in adults. We hypothesized that increased 5-HT signaling contributes to the pathogenesis of neonatal PH complicating BPD and neonatal lung injury. Read More

    Elastase Alters Contractility and Promotes an Inflammatory Synthetic Phenotype in Airway Smooth Muscle Tissues.
    Am J Physiol Lung Cell Mol Physiol 2017 Dec 6. Epub 2017 Dec 6.
    Cellular and Integrative Physiology, Indiana University School of Medicine, United States.
    Neutrophil elastase is secreted by inflammatory cells during airway inflammation and can elicit airway hyperactivity in vivo. Elastase can degrade multiple components of the extracellular matrix. We hypothesized that elastase might disrupt the connections between airway smooth muscle (ASM) cells and the extracellular matrix, and that this might have direct effects on ASM tissue responsiveness and inflammation. Read More

    Transcriptional Survey of Alveolar Macrophages in a Murine Model of Chronic Granulomatous Inflammation Reveals Common Themes with Human Sarcoidosis.
    Am J Physiol Lung Cell Mol Physiol 2017 Dec 6. Epub 2017 Dec 6.
    Medicine, University of Washington, United States.
    To advance our understanding of the pathobiology of sarcoidosis, we developed a multiwall carbon nanotube (MWCNT)-based murine model that shows marked histological and inflammatory signal similarities to this disease. In this study, we compared the alveolar macrophage transcriptional signatures of our animal model with human sarcoidosis to identify overlapping molecular programs. Whole-genome microarrays were used to assess gene expression of alveolar macrophages in 6 MWCNT-exposed and 6 control animals. Read More

    Roles of high-mobility group box 1 and thrombin in murine pulmonary fibrosis and the therapeutic potential of thrombomodulin.
    Am J Physiol Lung Cell Mol Physiol 2017 Dec 6. Epub 2017 Dec 6.
    Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan.
    Cross-talk between inflammation and coagulation plays important roles in acute or subacute progressive pulmonary fibrosis characterized by diffuse alveolar damage. Thrombomodulin is a physiological inhibitor of high-mobility group box 1 (HMGB1) and thrombin, and may be effective for this condition. This study investigated the roles of HMGB1 and thrombin in the pathophysiology of bleomycin-induced pulmonary fibrosis and the efficacy of recombinant human soluble thrombomodulin (rhTM). Read More

    Extracellular Retention of PDGF-B Directs Vascular Remodeling in Mouse Hypoxia-induced Pulmonary Hypertension.
    Am J Physiol Lung Cell Mol Physiol 2017 Dec 6. Epub 2017 Dec 6.
    Department of Molecular Medicine and Surgery, Karolinska University Hospital, Sweden.
    Pulmonary hypertension (PH) is a lethal condition and current vasodilator therapy has limited effect. Anti-proliferative strategies targeting platelet-derived growth factor (PDGF) receptors, such as imatinib, have generated promising results in animal studies. Imatinib is however a non-specific tyrosine kinase inhibitor and has in clinical studies caused unacceptable adverse events. Read More

    Over-production of growth differentiation factor 15 (GDF15) promotes human rhinovirus infection and virus-induced inflammation in the lung.
    Am J Physiol Lung Cell Mol Physiol 2017 Nov 30:ajplung003242017. Epub 2017 Nov 30.
    5 National Jewish health.
    Human rhinovirus (HRV) is the most common virus contributing to acute exacerbations of chronic obstructive pulmonary disease (COPD) nearly year-round, but the mechanisms have not been well elucidated. Recent clinical studies suggest that high levels of growth differentiation factor 15 (GDF15) protein in the blood are associated with an increased yearly rate of all-cause COPD exacerbations. Therefore, in the current study, we investigated whether GDF15 promotes HRV infection and virus-induced lung inflammation. Read More

    Chronic lung injury and impaired pulmonary function in a mouse model of acid ceramidase deficiency.
    Am J Physiol Lung Cell Mol Physiol 2017 Nov 22:ajplung002232017. Epub 2017 Nov 22.
    6 Medial college of Wisconsin.
    Farber Disease (FD) is a debilitating Lysosomal Storage Disorder (LSD) caused by a deficiency of acid ceramidase (ACDase) activity due to mutations in the gene ASAH1. Patients with ACDase deficiency may develop a spectrum of clinical phenotypes. Severe cases of FD are frequently associated with neurological involvement, failure to thrive, and respiratory complications. Read More

    Mesenchymal stem cells reduce hypoxia-induced apoptosis in alveolar epithelial cells by modulating HIF and ROS hypoxic signalings.
    Am J Physiol Lung Cell Mol Physiol 2017 Nov 22:ajplung001532017. Epub 2017 Nov 22.
    5 Université Paris 13.
    Distal lung diseases such as pulmonary fibrosis or acute lung injury are commonly associated with local alveolar hypoxia that may be deleterious through the stimulation of alveolar epithelial cell (AEC) apoptosis. In various murine models of alveolar injury, administration of allogenic human mesenchymal stem cells (hMSC) exerts an overall protective paracrine effect limiting lung inflammation and fibrosis. However, the precise mechanisms on lung cells themselves remain poorly understood. Read More

    MicroRNA-1 Is Decreased by Hypoxia and Contributes to the Development of Pulmonary Vascular Remodeling via Regulation of Sphingosine Kinase 1.
    Am J Physiol Lung Cell Mol Physiol 2017 Nov 22:ajplung000572017. Epub 2017 Nov 22.
    5 Indiana University.
    Sphingosine Kinase 1 (SphK1) upregulation is associated with pathologic pulmonary vascular remodeling in pulmonary arterial hypertension (PAH), but the mechanisms controlling its expression are undefined. In this study, we sought to characterize the regulation of SphK1 expression by microRNAs (miRs). In silico analysis of the SphK1-3'UTR identified several putative miR binding sites, with miR-1-3p (miR-1) being the most highly predicted target. Read More

    Accepting the challenge: maintaining AJP-Lung as the best place to publish basic and translational studies in lung biology and pathophysiology.
    Am J Physiol Lung Cell Mol Physiol 2017 Nov 16:ajplung.00488.2017. Epub 2017 Nov 16.
    University of Giessen and Marburg Lung Center (UGMLC)
    Rory E. Morty takes over from Sadis Matalon as Editor-in-Chief of the American Journal of Physiology - Lung Cellular and Molecular Physiology in January 2018. Here, key achievements and new and noteworthy additions to the editorial portfolio of the Journal will be reviewed. Read More

    Lumacaftor (VX-809) restores the ability of CF macrophages to phagocytose and kill Pseudomonas aeruginosa.
    Am J Physiol Lung Cell Mol Physiol 2017 Nov 16:ajplung004612017. Epub 2017 Nov 16.
    2 Geisel School of Medicine at Dartmouth.
    Cystic Fibrosis (CF), the most common lethal genetic disease in Caucasians, is characterized by chronic bacterial lung infection and excessive inflammation, which leads to progressive loss of lung function, and premature death. Although ivacaftor (VX-770) and the combination of ivacaftor and lumacaftor (VX-809) improve lung function in CF patients with the Gly551Asp and del508Phe mutation, respectively, the effects of these drugs on the function of human CF macrophages are unknown. Thus, studies were conducted to examine the effects of lumacaftor alone and in combination with ivacaftor (i. Read More

    Mast cell dependent IL-33/ST2 signaling is protective against the development of airway hyperresponsiveness in a house dust mite mouse model of asthma.
    Am J Physiol Lung Cell Mol Physiol 2017 Nov 16:ajplung002702017. Epub 2017 Nov 16.
    3 Karolinska Institutet.
    Interleukin-33 (IL-33) and its receptor ST2 have been influentially associated to the pathophysiology of asthma. Due to the divergent roles of IL-33 in regulating mast cell functions, there is a need to further characterize IL-33/ST2-dependent mast cell responses and their significance in the context of asthma. This study aimed to investigate how IL-33/ST2-dependent mast cell responses contribute to the development of airway hyperresponsiveness (AHR) and airway inflammation in a mouse model of house dust mite (HDM) induced asthma. Read More

    Prostanoid EP4 Agonist L-902,688 Activates PPARγ and Attenuates Pulmonary Arterial Hypertension.
    Am J Physiol Lung Cell Mol Physiol 2017 Nov 16:ajplung002452017. Epub 2017 Nov 16.
    1 Chang Gung University College of Medicine.
    Prostacyclin agonists that bind the prostacyclin receptor (IP) to stimulate cyclic adenosine monophosphate (cAMP) synthesis are effective vasodilators for the treatment of idiopathic pulmonary arterial hypertension (IPAH) but this signaling may occur through nuclear peroxisome proliferator-activated receptor-gamma (PPARγ). There is evidence of scant IP and PPARγ expression but stable prostanoid EP4 receptor (EP4) expression in IPAH patients. Both IP and EP4 functionally couple with stimulatory G protein (Gs), which activate signal transduction. Read More

    Renin-angiotensin system regulates pulmonary arterial smooth muscle cell migration in chronic thromboembolic pulmonary hypertension.
    Am J Physiol Lung Cell Mol Physiol 2017 Nov 9:ajplung005152016. Epub 2017 Nov 9.
    2 Capital Medical University, Beijing, China.
    Pulmonary arterial smooth muscle cell (PASMC) migration plays a key role in vascular remodeling which occurs during development of chronic thromboembolic pulmonary hypertension (CTEPH). Activation of the renin-angiotensin system (RAS) contributes to vascular remodeling observed in many diseases including idiopathic pulmonary arterial hypertension. However, the role of RAS imbalance in CTEPH has not been characterized. Read More

    Limited role of kininogen in the host response during gram-negative pneumonia derived sepsis.
    Am J Physiol Lung Cell Mol Physiol 2017 Nov 9:ajplung002882017. Epub 2017 Nov 9.
    1 Academic Medical Center.
    High molecular weight kininogen (HK), together with Factor XI, Factor XII and prekallikrein, is part of the contact system, which has proinflammatory, prothrombotic and vasoactive properties. We hypothesized that HK plays a role in the host response during pneumonia derived sepsis. To this end mice were depleted of kininogen (KNG) to plasma HK levels of 28% of normal by repeated treatment with a specific antisense oligonucleotide (KNG ASO) for three weeks prior to infection with the common human sepsis pathogen Klebsiella pneumoniae via the airways. Read More

    NLRP3 Inflammasome Activation in Aged Macrophages is diminished during Streptococcus pneumoniae Infection.
    Am J Physiol Lung Cell Mol Physiol 2017 Nov 2:ajplung003932017. Epub 2017 Nov 2.
    1 Weill Cornell Medical College.
    Pneumococcal infections are the 8th leading cause of death in the United States and it is estimated that older patients (>65 years of age) account for the most serious cases. The goal of our current study is to understand the impact of biological aging on innate immune responses to Streptococcus pneumoniae, a causative agent of bacterial pneumonia. Using in vitro and in vivo aged murine models, our findings demonstrate that age-enhanced unfolded protein responses (UPR) contribute to diminished inflammasome assembly and activation during S. Read More

    The emerging role of angiogenesis in adaptive and maladaptive right ventricular remodeling in pulmonary hypertension.
    Am J Physiol Lung Cell Mol Physiol 2017 Nov 2:ajplung003742017. Epub 2017 Nov 2.
    1 Indiana University School of Medicine.
    Right ventricular (RV) function is the primary prognostic factor for both morbidity and mortality in pulmonary hypertension (PH). RV hypertrophy is initially an adaptive physiological response to increased overload; however, with persistent and/or progressive afterload increase, this response frequently transitions to more pathological maladaptive remodeling. The mechanisms and disease processes underlying this transition are mostly unknown. Read More

    Docosahexaenoic acid enhances amphiregulin-mediated bronchial epithelial cell repair processes following organic dust exposure.
    Am J Physiol Lung Cell Mol Physiol 2017 Nov 2:ajplung002732017. Epub 2017 Nov 2.
    1 University of Nebraska Medical Center.
    Injurious dust exposures in the agricultural workplace involve the release of inflammatory mediators and activation of epidermal growth factor receptor (EGFR) in the respiratory epithelium. Amphiregulin, an EGFR ligand, mediates tissue repair and wound healing in the lung epithelium. Omega-3 fatty acids such as docosahexaenoic acid (DHA) are also known modulators of repair and resolution of inflammatory injury. Read More

    The free fatty acid receptor 1 promotes airway smooth muscle cell proliferation through MEK/ERK and PI3K/Akt signaling pathways.
    Am J Physiol Lung Cell Mol Physiol 2017 Nov 2:ajplung001292017. Epub 2017 Nov 2.
    1 Tohoku University Graduate School of Dentistry.
    Obesity is a risk factor for asthma and influences airway hyperresponsiveness, which is in part modulated by airway smooth muscle proliferative remodeling. Plasma free fatty acids (FFAs) levels are elevated in obese individuals, and long-chain FFAs act as endogenous ligands for the free fatty acid receptor 1 (FFAR1), which couples to both Gq and Gi proteins. We examined whether stimulation of FFAR1 induces airway smooth muscle cell proliferation through classical MEK/ERK and/or PI3K/Akt signaling pathways. Read More

    Docosahexaenoic acid inhibits monocrotaline-induced pulmonary hypertension via attenuating endoplasmic reticulum stress and inflammation.
    Am J Physiol Lung Cell Mol Physiol 2017 Nov 2:ajplung000462017. Epub 2017 Nov 2.
    3 Affiliated Hospital of Jiangsu University.
    Endoplasmic reticulum (ER) stress and inflammation contribute to pulmonary hypertension (PH) pathogenesis. Previously, we confirmed docosahexaenoic acid (DHA) could improve hypoxic-induced PH. However, little is known about the link between DHA and monocrotaline (MCT)-induced PH. Read More

    Autophagy Inhibitor 3-Methyladenine Protects against Endothelial Cell Barrier Dysfunction in Acute Lung Injury.
    Am J Physiol Lung Cell Mol Physiol 2017 Oct 26:ajplung005552016. Epub 2017 Oct 26.
    1 University of Rochester.
    Autophagy is an evolutionarily conserved cellular process that facilitates the continuous recycling of intracellular components (organelles and proteins) and provides an alternative source of energy when nutrients are scarce. Recent studies have implicated autophagy in many disorders including pulmonary diseases. However, the role of autophagy in endothelial cell (EC) barrier dysfunction and its relevance in the context of acute lung injury (ALI) remains uncertain. Read More

    Simvastatin Decreases Hyperoxic Oxygen-Induced Acute Lung Injury by Upregulating eNOS.
    Am J Physiol Lung Cell Mol Physiol 2017 Oct 26:ajplung005202016. Epub 2017 Oct 26.
    1 Institute of Naval Medical Research.
    Statins, which are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase competitive inhibitors, not only lower blood cholesterol, but also exert pleiotropic and beneficial effects in various diseases. However, the effects of statins on acute lung injury (ALI) induced by hyperbaric oxygen (HBO) have not been investigated. The present study is the first to investigate the effects of simvastatin in ALI induced by HBO in 8 - 9 week old C57BL/6 mice exposed to 0. Read More

    Lung disease phenotypes caused by over-expression of combinations of alpha, beta, and gamma subunits of the epithelial sodium channel in mouse airways.
    Am J Physiol Lung Cell Mol Physiol 2017 Oct 26:ajplung003822017. Epub 2017 Oct 26.
    2 The University of North Carolina at Chapel Hill.
    The epithelial Na+ channel (ENaC) regulates airway surface hydration. In mouse airways, ENaC is composed of three subunits, alpha (α), beta (β), and gamma (γ), which are differentially expressed (α > β > γ). Airway-targeted overexpression of the β subunit results in Na+ hyperabsorption causing airway surface dehydration, hyperconcentrated mucus with delayed clearance, lung inflammation, and perinatal mortality. Read More

    Autophagy and the Unfolded Protein Response Promote Pro-fibrotic Effects of TGFβ1 in Human Lung Fibroblasts.
    Am J Physiol Lung Cell Mol Physiol 2017 Oct 26:ajplung003722017. Epub 2017 Oct 26.
    1 University of Manitoba.
    Background: Idiopathic pulmonary fibrosis (IPF) is a lethal fibrotic lung disease in adults with limited treatment options. Autophagy and the unfolded protein response (UPR), fundamental processes induced by cell stress, are dysregulated in lung fibroblasts and epithelial cells from humans with IPF.

    Methods: Human primary cultured lung parenchymal and airway fibroblasts from non-IPF and IPF donors were stimulated with TGFβ1 with or without the inhibitors of autophagy or UPR (IRE1α inhibitor). Read More

    Endothelial HIF-2α Contributes to Severe Pulmonary Hypertension by Inducing Endothelial-to-Mesenchymal Transition.
    Am J Physiol Lung Cell Mol Physiol 2017 Oct 26:ajplung000962017. Epub 2017 Oct 26.
    2 University of Arizona.
    Pulmonary vascular remodeling characterized by concentric wall thickening and intraluminal obliteration contributes to the elevated PVR in patients with IPAH. Here we report that increased HIF-2α in lung vascular endothelial cells (LVEC) under normoxic conditions is involved in the development of pulmonary hypertension (PH) by inducing endothelial-to-mesenchymal transition (EndMT), which subsequently results in vascular remodeling and occlusive lesions. We observed significant EndMT and markedly increased expression of SNAI, an inducer of EndMT, in LVEC from IPAH patients and PH animals compared with controls. Read More

    12-lipoxygenase and 12-hydroxyeicosatetraenoic acid regulate hypoxic angiogenesis and survival of pulmonary artery endothelial cells via PI3K/Akt pathway.
    Am J Physiol Lung Cell Mol Physiol 2017 Oct 26:ajplung000492017. Epub 2017 Oct 26.
    2 Harbin Medical University (Daqing).
    Dysfunction and injury of endothelial cells play critical roles in the pulmonary arterial hypertension, which including the aberrant proliferation, suppressed apoptosis and excessive angiogenesis.12-lipoxygenase and 12-hydroxyeicosatetraenoic acid pathway, which has been considered as a crucial mediator, elevates pulmonary vascular resistance and pulmonary arterial pressure. However, the mechanisms underlying the bioactivity of 12-hydroxyeicosatetraenoic acid in pulmonary vasculature especially in endothelial cells are still elusive. Read More

    Neutrophil elastase increases airway ceramide levels via upregulation of serine palmitoyltransferase.
    Am J Physiol Lung Cell Mol Physiol 2017 Oct 12:ajplung.00322.2017. Epub 2017 Oct 12.
    Children's Hospital of Richmond at Virginia Commonwealth University
    Altered sphingolipid metabolism is associated with increased inflammation; however, the impact of inflammatory mediators, including neutrophil elastase (NE), on airway sphingolipid homeostasis remains unknown. Using a well-characterized mouse model of NE oropharyngeal aspiration, we investigated a potential link between NE-induced airway inflammation and increased synthesis of various classes of sphingolipids, including ceramide species. Sphingolipids in bronchoalveolar lavage fluids (BAL) were identified and quantified using reverse phase high-performance liquid chromatography/electrospray ionization tandem mass spectrometry analysis. Read More

    Ion channels of the lung and their role in disease pathogenesis.
    Am J Physiol Lung Cell Mol Physiol 2017 Nov 12;313(5):L859-L872. Epub 2017 Oct 12.
    Department of Cell, Developmental, and Integrative Biology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama;
    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. Read More

    Toll-like receptor 2 and 4 have Opposing Roles in the Pathogenesis of Cigarette Smoke-induced Chronic Obstructive Pulmonary Disease.
    Am J Physiol Lung Cell Mol Physiol 2017 Oct 12:ajplung001542017. Epub 2017 Oct 12.
    1 University of Newcastle.
    Chronic Obstructive Pulmonary Disease (COPD) is the third leading cause of morbidity and death and imposes major socioeconomic burdens globally. It is a progressive and disabling condition that severely impairs breathing and lung function. There is a lack of effective treatments for COPD, which is a direct consequence of the poor understanding of the underlying mechanisms involved in driving the pathogenesis of the disease. Read More

    Intranasal administration of recombinant progranulin inhibits bronchial smooth muscle hyperresponsiveness in mouse allergic asthma.
    Am J Physiol Lung Cell Mol Physiol 2017 Oct 5:ajplung.00575.2016. Epub 2017 Oct 5.
    Hoshi University.
    Progranulin (PGRN) is a growth factor with multiple biological functions, and has been suggested as an endogenous inhibitor of TNFα-mediated signaling. TNFα is believed as one of the important mediators of the pathogenesis of asthma, including airway hyperresponsiveness (AHR). In the present study, effects of recombinant PGRN on the TNFα-mediated signaling and the antigen-induced hyper-contractility were examined in bronchial smooth muscles (BSMs) both in vitro and in vivo. Read More

    Evaluation of a SPLUNC1-Derived Peptide for the Treatment of Cystic Fibrosis Lung Disease.
    Am J Physiol Lung Cell Mol Physiol 2017 Oct 5:ajplung.00546.2016. Epub 2017 Oct 5.
    University of North Carolina at Chapel Hill
    In cystic fibrosis (CF) lungs, epithelial Na+ channel (ENaC) hyperactivity causes a reduction in airway surface liquid (ASL) volume, leading to decreased mucocilliary clearance and lung damage. Inhibition of ENaC is an attractive therapeutic option. However, ENaC antagonists have failed clinically due to off-target renal effects. Read More

    An epoxide hydrolase secreted by Pseudomonas aeruginosa decreases mucociliary transport and hinders bacterial clearance from the lung.
    Am J Physiol Lung Cell Mol Physiol 2017 Oct 5:ajplung.00383.2017. Epub 2017 Oct 5.
    Geisel School of Medicine at Dartmouth
    The opportunistic pathogen Pseudomonas aeruginosa colonizes the lungs of susceptible individuals by deploying virulence factors targeting host defenses. The secreted CFTR inhibitory factor (Cif) dysregulates the endocytic recycling of CFTR and thus reduces CFTR abundance in host epithelial membranes. We have postulated that the decrease in ion secretion mediated by Cif would slow mucociliary transport and decrease bacterial clearance from the lungs. Read More

    Acidosis Exacerbates in vivo IL-1-Dependent Inflammatory Responses and Neutrophil Recruitment During Pulmonary Pseudomonas aeruginosa Infection.
    Am J Physiol Lung Cell Mol Physiol 2017 Oct 5:ajplung003382017. Epub 2017 Oct 5.
    2 Dartmouth Medical School.
    Acidic microenvironments commonly occur at sites of inflammation and bacterial infections. In the context of a Pseudomonas aeruginosa infection, we previously demonstrated that acidosis enhances the cellular proinflammatory IL-1β response in vitro. However, how pH alterations affect in vivo IL-1β responses and subsequent IL-1 driven inflammation during infection with P. Read More

    Use of proper statistical techniques for research studies with small samples.
    Am J Physiol Lung Cell Mol Physiol 2017 Nov 5;313(5):L873-L877. Epub 2017 Oct 5.
    Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama
    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. Read More

    ATP catabolism by tissue non-specific alkaline phosphatase contributes to development of ARDS in influenza-infected mice.
    Am J Physiol Lung Cell Mol Physiol 2017 Oct 5:ajplung.00149.2017. Epub 2017 Oct 5.
    The Ohio State University
    Influenza A viruses are highly contagious respiratory pathogens that are responsible for significant morbidity and mortality worldwide on an annual basis. We have shown previously that influenza infection of mice leads to increased ATP and adenosine accumulation in the airway lumen. Moreover, we demonstrated that A1-adenosine receptor activation contributes significantly to influenza-induced acute respiratory distress syndrome (ARDS). Read More

    Activation of the sweet taste receptor, T1R3, by the artificial sweetener sucralose regulates the pulmonary endothelium.
    Am J Physiol Lung Cell Mol Physiol 2017 Sep 28:ajplung.00490.2016. Epub 2017 Sep 28.
    Anglia Ruskin University
    A hallmark of acute respiratory distress syndrome (ARDS) is pulmonary vascular permeability. In these settings, loss of barrier integrity is mediated by cell-contact disassembly and actin-remodelling. Studies into molecular mechanisms responsible for improving microvascular barrier function are therefore vital in the development of therapeutic targets for reducing vascular permeability in ARDS. Read More

    Human lung branching morphogenesis is orchestrated by the spatio-temporal distribution of ACTA2, SOX2 and SOX9.
    Am J Physiol Lung Cell Mol Physiol 2017 Sep 28:ajplung.00379.2017. Epub 2017 Sep 28.
    Children's Hospital Los Angeles
    Lung morphogenesis relies on a number of important processes including proximal-distal patterning, cell proliferation, migration and differentiation, as well as epithelial-mesenchymal interactions. In mouse lung development, SOX2+ cells are localized in the proximal epithelium whereas SOX9+ cells are present in the distal epithelium. We show that in human lung, expression of these transcription factors differs, in that during the pseudoglandular stage distal epithelial progenitors at the tips co-express SOX2 and SOX9. Read More

    Recent advances in our understanding of the mechanisms of late lung development and bronchopulmonary dysplasia.
    Am J Physiol Lung Cell Mol Physiol 2017 Dec 28;313(6):L1101-L1153. Epub 2017 Sep 28.
    Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany; and
    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 conducting vessels, respectively, generates steep oxygen and carbon dioxide concentration gradients across the alveolo-capillary barrier, providing ideal conditions for effective diffusion of both gases during breathing. Read More

    TBX4 is involved in the super-enhancer-driven transcriptional programs underlying features specific to lung fibroblasts.
    Am J Physiol Lung Cell Mol Physiol 2017 Sep 28:ajplung.00193.2017. Epub 2017 Sep 28.
    Univ. of Tokyo, Faculty of Medicine.
    Lung fibroblasts participate in the pathogenesis of respiratory diseases, including lung cancer and pulmonary fibrosis. Although fibroblasts are ubiquitous constituents of various organs, their cellular diversity among different organs has been poorly characterized. Here, we aimed to investigate the distinct gene signature of lung fibroblasts that represents its pulmonary origin, and the underlying gene regulatory networks. Read More

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