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    4692 results match your criteria American Journal of Physiology - Lung Cellular and Molecular Physiology[Journal]

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    Versican is Produced by Trif- and Type I Interferon-Dependent Signaling in Macrophages and Contributes to Fine-Control of Innate Immunity in Lungs.
    Am J Physiol Lung Cell Mol Physiol 2017 Sep 14:ajplung.00353.2017. Epub 2017 Sep 14.
    Univeristy of Washington
    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 (BMDM) from mice lacking specific Toll-like receptors (TLR), TLR adaptor molecules or the type I interferon receptor (IFNAR1). Read More

    Invariant natural killer T cells promote immunogenic maturation of lung dendritic cells in mouse models of asthma.
    Am J Physiol Lung Cell Mol Physiol 2017 Sep 14:ajplung.00340.2016. Epub 2017 Sep 14.
    Department of Respiratory Medicine, Renmin Hospital of Wuhan University, Wuhan 430060, China
    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, co-culture experiments, and adoptive transfer of iNKT cells in mouse models of asthma. Our data showed that iNKT cell deficiency could downregulate surface maturation markers and proinflammatory cytokine secretion of LDCs from a mouse model of asthma. Read More

    Exposure of Neonatal Mice to Bromine Impairs Their Alveolar Development and Lung Function.
    Am J Physiol Lung Cell Mol Physiol 2017 Sep 14:ajplung.00315.2017. Epub 2017 Sep 14.
    University of Alabama at Birmingham.
    The halogen bromine (Br2) is used extensively in industry and stored and transported in large quantities. Its accidental or malicious release into the atmosphere has resulted in significant casualties. The pathophysiology of Br2-induced lung injury has been studied in adult animals, but the consequences of Br2 exposure to the developing lung are completely unknown. Read More

    Element-based prognostics of occupational pneumoconiosis using micro-proton-induced X-ray emission analysis.
    Am J Physiol Lung Cell Mol Physiol 2017 Sep 14:ajplung.00009.2017. Epub 2017 Sep 14.
    Tongji University School of Medicine
    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 2D 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, while symptoms in some welders were alleviated after five years, as determined by comparing percent vital capacity (VC%) and forced expiratory volume in the first second over forced vital capacity (FEV1. Read More

    Childhood tolerance of severe influenza: a mortality analysis in mice.
    Am J Physiol Lung Cell Mol Physiol 2017 Sep 7:ajplung.00364.2017. Epub 2017 Sep 7.
    Harvard T.H. Chan School of Public Health
    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. Read More

    Opsin 3 and 4 Mediate Light-Induced Pulmonary Vasorelaxation that is Potentiated by G-Protein Receptor Kinase 2 Inhibition.
    Am J Physiol Lung Cell Mol Physiol 2017 Sep 7:ajplung.00091.2017. Epub 2017 Sep 7.
    The Johns Hopkins University
    We recently demonstrated that blue light induces vasorelaxation in the systemic mouse circulation, a phenomenon mediated by the non-visual G protein-coupled receptor (GPCR) melanopsin (opsin 4; Opn4). Here we tested the hypothesis that non-visual opsins mediate photorelaxation in the pulmonary circulation. We discovered Opsin 3 (Opn3), Opn4, and G-protein coupled receptor kinase 2 (GRK2) in rat pulmonary arteries (PAs) and in pulmonary arterial smooth muscle cells (PASMCs), where the opsins interact directly with GRK2 as demonstrated with a proximity ligation assay. Read More

    Targeting Plasminogen Activator Inhibitor 1 in Tetracycline-Induced Pleural Injury in Rabbits.
    Am J Physiol Lung Cell Mol Physiol 2017 Aug 31:ajplung.00579.2016. Epub 2017 Aug 31.
    University of Texas Health Science Center at Tyler
    Elevated active plasminogen activator inhibitor 1 (PAI-1) has an adverse effect on the outcomes of intrapleural fibrinolytic therapy (IPFT) in tetracycline-induced pleural injury in rabbits. In order to enhance IPFT with prourokinase (scuPA), two mechanistically distinct approaches to targeting PAI-1 were tested: slowing its reaction with urokinase (uPA) and mAb-mediated PAI-1 inactivation. Removing positively charged residues at the "PAI-1 docking site" ((179)RHRGGS(184)→(179)AAAAAA(184)) of uPA results in a 60-fold decrease in the rate of inhibition by PAI-1. Read More

    Blockade of extracellular heat shock protein 90 alpha by 1G6-D7 attenuates pulmonary fibrosis through inhibiting ERK signaling.
    Am J Physiol Lung Cell Mol Physiol 2017 Aug 31:ajplung.00489.2016. Epub 2017 Aug 31.
    Southern Medicial University
    Pulmonary fibrosis is characterized by lung fibroblast activation and ECM deposition and has a poor prognosis.Heat shock protein 90 (Hsp90) participates in organ fibrosis and extracellular Hsp90α (eHsp90α) promotes fibroblast activation and migration. This study aimed to investigate whether a selective anti-Hsp90α monoclonal antibody, 1G6-D7, could attenuate lung fibrosis and whether 1G6-D7 presents protective effect by inactivating profibrotic pathway. Read More

    IL-17 in the lung: The Good, the Bad, and the Ugly.
    Am J Physiol Lung Cell Mol Physiol 2017 Aug 31:ajplung.00344.2017. Epub 2017 Aug 31.
    University of Michigan, MI, USA.
    The IL-17 family of cytokines has emerged over the last two decades as a pleiotropic group of molecules that function in a wide variety of both beneficial and detrimental (pathologic) processes mainly in mucosal barrier tissue. The beneficial effects of IL-17 expression are especially important in the lung where exposure to foreign agents is abundant. IL-17A plays an important role in protection from both extracellular bacteria and fungi as well as viruses that infect cells of the mucosal tracts. Read More

    The respiratory tract microbial biogeography in alcohol use disorder.
    Am J Physiol Lung Cell Mol Physiol 2017 Aug 31:ajplung.00277.2017. Epub 2017 Aug 31.
    Louisiana State University Health Sciences Center
    Rationale: Individuals with alcohol use disorders (AUDs) are at an increased risk of pneumonia and acute respiratory distress syndrome. Data of the lung microbiome in the setting of AUDs are lacking. The objective of this study was to determine the microbial biogeography of the upper and lower respiratory tract in individuals with AUDs compared to non-AUD subjects. Read More

    IPF lung fibroblasts have a senescent phenotype.
    Am J Physiol Lung Cell Mol Physiol 2017 Aug 31:ajplung.00220.2017. Epub 2017 Aug 31.
    University of Pittsburgh
    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 (hLF) 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 hLF isolated from IPF lungs compared to age-matched controls. Read More

    IL-8 Mediates Idiopathic Pulmonary Fibrosis Mesenchymal Progenitor Cell Fibrogenicity.
    Am J Physiol Lung Cell Mol Physiol 2017 Aug 31:ajplung.00200.2017. Epub 2017 Aug 31.
    University of Minnesota School of Medicine
    Idiopathic Pulmonary Fibrosis (IPF) is a progressive fibrotic lung disease, but the mechanisms driving progression remain incompletely defined. We previously reported that the IPF lung harbors fibrogenic mesenchymal progenitor cells (MPCs), which serve as a cell-of-origin for IPF fibroblasts. Proliferating IPF MPCs are located at the periphery of fibroblastic foci in an active cellular front at the interface between the myofibroblast rich focus core and adjacent normal alveolar structures. Read More

    Novel therapeutic roles for surfactant-inositols and -phosphatidylglycerols in a neonatal piglet ARDS model. A translational study.
    Am J Physiol Lung Cell Mol Physiol 2017 Aug 31:ajplung.00128.2017. Epub 2017 Aug 31.
    Universitätsklinikum Schleswig-Holstein (UKSH), Campus Kiel
    The biological and immune-protective properties of surfactant-derived phospholipids and phospholipid-subfractions in the context of neonatal inflammatory lung disease are widely unknown. Using a porcine neonatal triple-hit ARDS model (repeated airway lavage, overventilation, LPS instillation into airways), we assessed whether the supplementation of surfactant (poractant alfa, S) with inositol-derivatives (inositol-1,2,6-trisphosphate, IP3; phosphatidylinositol-3,5-bisphosphate, PIP2) or phosphatidylglycerol-subfractions (16:0/18:1-POPG; 18:1/18:1-DOPG) would result in improved clinical parameters, and sought to characterize changes in key inflammatory pathways behind these improvements. Within 72 h of mechanical ventilation, the oxygenation index (S+IP3/PIP2/POPG), the ventilation efficiency index (S+IP3/POPG), the compliance (S+IP3/POPG) and the resistance (S+POPG) of the respiratory system, and the extra-vascular lung water index (S+IP3/POPG) significantly improved compared to S treatment alone. Read More

    Alcohol Abuse is Associated with Enhanced Pulmonary and Systemic Xanthine Oxidoreductase Activity.
    Am J Physiol Lung Cell Mol Physiol 2017 Aug 24:ajplung.00570.2016. Epub 2017 Aug 24.
    University of Colorado Denver School of Medicine
    The 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 enhancing 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. Read More

    Epigenetic Changes by DNA methylation in Chronic and Intermittent Hypoxia.
    Am J Physiol Lung Cell Mol Physiol 2017 Aug 24:ajplung.00325.2017. Epub 2017 Aug 24.
    The University of Chicago
    DNA methylation of cytosine residues is a well-studied epigenetic change, which regulates gene transcription by altering accessibility for transcription factors. Hypoxia is a pervasive stimulus that affects many physiological processes. The circulatory and respiratory systems adapt to chronic sustained hypoxia, such as that encountered during a high altitude sojourn. Read More

    Levosimendan prevents bronchoconstriction and adverse respiratory tissue mechanical changes in rabbits.
    Am J Physiol Lung Cell Mol Physiol 2017 Aug 24:ajplung.00213.2017. Epub 2017 Aug 24.
    University of Szeged
    Levosimendan has a calcium-sensitizing effect in the myocardium and opens adenosine-triphosphate-sensitive potassium channels (KATP) in vascular smooth muscle. Since 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). Read More

    The beginnings of cardiac catheterization, and the resulting impact on pulmonary medicine.
    Am J Physiol Lung Cell Mol Physiol 2017 Aug 24:ajplung.00133.2017. Epub 2017 Aug 24.
    University of California San Diego
    The early history of cardiac catheterization has many interesting features. First, although it would be natural to assume that the procedure was initiated by cardiologists, two of the three people who shared the Nobel Prize for the discovery were pulmonologists, while the third was a urologist. The primary objective of the pulmonologists, André Cournand and Dickinson Richards, was to obtain mixed venous blood from the right heart so that they could use to use the Fick principle to calculate total pulmonary blood flow. Read More

    Hyperoxia treatment of TREK-1/TREK-2/TRAAK-deficient mice is associated with a reduction in surfactant proteins.
    Am J Physiol Lung Cell Mol Physiol 2017 Aug 24:ajplung.00121.2017. Epub 2017 Aug 24.
    University of Tennessee Health Science Center.
    We previously proposed a role for the 2-pore domain potassium (K2P) channel TREK-1 in hyperoxia (HO)-induced lung injury. To determine whether redundancy between the 3 TREK isoforms (TREK-1, TREK-2, TRAAK) could protect from HO-induced injury, we now examined the effect of deletion of all 3 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 ko) mice to either room air, 72 hours HO, MV (high and low tidal volume), or a combination of HO+MV, and measured quasi-static lung compliance, BAL protein concentration, histologic lung injury scores (LIS), cellular apoptosis, and cytokine levels. Read More

    Platelet CLEC-2 protects against lung injury via effects of its ligand podoplanin on inflammatory alveolar macrophages in the mouse.
    Am J Physiol Lung Cell Mol Physiol 2017 Aug 24:ajplung.00023.2017. Epub 2017 Aug 24.
    University of Birmingham.
    There is no therapeutic intervention proven to prevent the acute respiratory syndrome (ARDS). Novel mechanistic insights into the pathophysiology of ARDS are therefore required. Platelets are implicated in regulating many of the pathogenic processes which occur during ARDS, however the mechanisms remain elusive. Read More

    Sexual dimorphism of the pulmonary transcriptome in neonatal hyperoxic lung injury: identification of angiogenesis as a key pathway.
    Am J Physiol Lung Cell Mol Physiol 2017 Aug 17:ajplung.00230.2017. Epub 2017 Aug 17.
    Baylor College of Medicinei
    Bronchopulmonary dysplasia (BPD) is characterized by impaired alveolar secondary septation and vascular growth. Exposure to high concentrations of oxygen (hyperoxia) contributes to the development of BPD. Male sex is considered an independent risk factor for the development of BPD. Read More

    Fra-2 negatively regulates postnatal alveolar septation by modulating myofibroblast function.
    Am J Physiol Lung Cell Mol Physiol 2017 Aug 17:ajplung.00062.2017. Epub 2017 Aug 17.
    University of California San Francisco
    Mice that globally over-express 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 over-express Fra-2 specifically in these cells types (α-SMA-rtTA; tetO-Fra-2). Surprisingly, these mice did not develop vascular remodeling or pulmonary fibrosis, but developed a spontaneous emphysema-like phenotype characterized by alveolar enlargement. Read More

    Endothelial cell-related autophagic pathways in Sugen/hypoxia-exposed pulmonary arterial hypertensive rats.
    Am J Physiol Lung Cell Mol Physiol 2017 Aug 10:ajplung.00527.2016. Epub 2017 Aug 10.
    Chiba University.
    Pulmonary arterial hypertension (PAH) is characterized by progressive obstructive remodeling of pulmonary arteries. However, no reports have described the causative role of the autophagic pathway in pulmonary vascular endothelial cell (EC) alterations associated with PAH. 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. Read More

    PRESERVED RIGHT VENTRICULAR INTEGRITY IN A NEW TELEMETRIC RAT MODEL OF SEVERE PULMONARY HYPERTENSION.
    Am J Physiol Lung Cell Mol Physiol 2017 Aug 10:ajplung.00278.2017. Epub 2017 Aug 10.
    Medical University of Vienna
    Telemetric monitoring of hemodynamic parameters has become an established standard in experimental models of pulmonary arterial hypertension (PAH). To that purpose, a dedicated catheter is usually implanted through the right ventricular wall of study animals. Drawbacks of this standard technique are: obtained pressures are from the right ventricle and therefore only surrogates for pulmonary arterial pressures, and furthermore, right ventricular myocardium is always damaged to a certain degree. Read More

    Aquaporin 1-mediated changes in pulmonary arterial smooth muscle cell migration and proliferation involve β-catenin.
    Am J Physiol Lung Cell Mol Physiol 2017 Aug 10:ajplung.00247.2016. Epub 2017 Aug 10.
    Johns Hopkins University
    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 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. Read More

    Metabolic characterization and RNA profiling reveal glycolytic dependence of pro-fibrotic phenotype of alveolar macrophages in lung fibrosis.
    Am J Physiol Lung Cell Mol Physiol 2017 Aug 10:ajplung.00235.2017. Epub 2017 Aug 10.
    University of Alabama at Birmingham
    Metabolic reprogramming has been intrinsically linked to macrophage activation. Alveolar macrophages are known to play an important role in the pathogenesis of pulmonary fibrosis. However, systematic characterization of expression profile in these cells is still lacking. Read More

    Benefits of Oxytocin Administration in Obstructive Sleep Apnea.
    Am J Physiol Lung Cell Mol Physiol 2017 Aug 10:ajplung.00206.2017. Epub 2017 Aug 10.
    George Washington University
    Activation of oxytocin receptors has shown benefits in animal models of Obstructive Sleep Apnea (OSA). We tested if nocturnal oxytocin administration could have beneficial effects in OSA patients. 8 patients diagnosed with OSA were administered intranasal oxytocin (40 i. Read More

    Oxygen-dependent changes in lung development do not affect epithelial infection with influenza A virus.
    Am J Physiol Lung Cell Mol Physiol 2017 Aug 10:ajplung.00203.2017. Epub 2017 Aug 10.
    The University of Rochester
    Infants born prematurely often require supplemental oxygen that 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 influenza A virus (IAV (A/Hong Kong/X31) H3N2) as defined by persistent inflammation, pulmonary fibrosis, and mortality. Read More

    CYP2E1 regulates the development of radiation-induced pulmonary fibrosis via ER stress- and ROS-dependent mechanisms.
    Am J Physiol Lung Cell Mol Physiol 2017 Aug 10:ajplung.00144.2017. Epub 2017 Aug 10.
    Pusan National University, Republic of Korea
    Radiation-induced pulmonary fibrosis (RIPF) is one of the most common side effects of lung cancer radiotherapy. 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. Read More

    Pollen-induced oxidative DNA damage response regulates miRNAs controlling allergic inflammation.
    Am J Physiol Lung Cell Mol Physiol 2017 Aug 10:ajplung.00141.2017. Epub 2017 Aug 10.
    Univ Texas Medical Branch at Galveston
    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 oxidative genomic base damage is 8-oxo-7,8-dihydroguanine (8-oxoG), which is removed from DNA by 8-oxoguanine DNA glycosylase1 (OGG1). Read More

    LungMAP: The Molecular Atlas of Lung Development Program.
    Am J Physiol Lung Cell Mol Physiol 2017 Aug 10:ajplung.00139.2017. Epub 2017 Aug 10.
    RTI International.
    The National Heart Lung and Blood Institute is funding an effort to create a molecular atlas of the developing lung (LungMAP) to serve as a research resource and public education tool. The lung is a complex organ with lengthy development time driven by interactive gene networks and dynamic crosstalk among multiple cell types to control and coordinate lineage specification, cell proliferation, differentiation, migration, morphogenesis and injury repair. A better understanding of the processes that regulate lung development, particularly alveologenesis, will have significant impact on survival rates for premature infants born with incomplete lung development and will facilitate lung injury repair and regeneration in adults. Read More

    Alternative Pre-mRNA Splicing of Toll-Like Receptor Signaling Components in Peripheral Blood Mononuclear Cells from ARDS Patients.
    Am J Physiol Lung Cell Mol Physiol 2017 Aug 3:ajplung.00247.2017. Epub 2017 Aug 3.
    National Jewish Health
    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. Read More

    Influenza virus infection alters ion channel function of Airway and alveolar cells: Mechanisms and physiological sequelae.
    Am J Physiol Lung Cell Mol Physiol 2017 Aug 3:ajplung.00244.2017. Epub 2017 Aug 3.
    University of Alabama at Birmingham
    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 pericilary fluid (PCL) and alveolar lining fluid (ALF) layers. Read More

    Platelet-derived growth factor receptor-alpha (PDGFRα) and Ras-related C3 botulinum toxin substrate-1 (Rac1) regulate mechano-responsiveness of lung fibroblasts.
    Am J Physiol Lung Cell Mol Physiol 2017 Aug 3:ajplung.00185.2017. Epub 2017 Aug 3.
    University of Iowa Carver College of Medicine.
    Platelet-derived growth factor (PDGF)-A, which only signals through PDGF-receptor-alpha (PDGFRα) is required for secondary alveolar septal formation. Although PDGFRα distinguishes mesenchymal progenitor cells during the saccular stage, PDGFRα-expressing alveolar cells persist through adulthood. PDGF-A sustains proliferation, limits apoptosis, and maintains alpha-smooth muscle actin (αSMA) containing alveolar cells, which congregate at the alveolar entry ring at postnatal day (P)12. Read More

    Repetitive Intradermal Bleomycin Injections Evokes T Helper Cell 2 Cytokine-driven Pulmonary Fibrosis.
    Am J Physiol Lung Cell Mol Physiol 2017 Aug 3:ajplung.00184.2017. Epub 2017 Aug 3.
    Cincinnati Children's Hospital Medical Center
    IL-4 and IL-13 are major T helper cell (Th) 2 cytokines implicated in the pathogenesis of several lung diseases, including pulmonary fibrosis. In this study, using a novel repetitive intradermal bleomycin model in which mice develop extensive lung fibrosis and a progressive decline in lung function compared to saline-treated control mice, we investigated profibrotic functions of Th2 cytokines. To determine the role of IL-13 signaling in the pathogenesis of bleomycin-induced pulmonary fibrosis, wild-type, IL-13, and IL-4Rα-deficient mice were treated with bleomycin, and lungs were assessed for changes in lung function and pulmonary fibrosis. Read More

    Transglutaminase 2 in Pulmonary and Cardiac Tissue Remodeling in Experimental Pulmonary Hypertension.
    Am J Physiol Lung Cell Mol Physiol 2017 Aug 3:ajplung.00170.2017. Epub 2017 Aug 3.
    Tufts Medical Center
    Tissue matrix remodeling and fibrosis leading to loss of pulmonary arterial and right ventricular compliance are important features of both experimental and clinical pulmonary hypertension (PH). We have previously reported that transglutaminase 2 (TG2) is involved in PH development while others have shown it to be a crosslinking enzyme that participates in remodeling of extracellular matrix in fibrotic diseases in general. In the present studies, we used a mouse model of experimental PH (Sugen 5416 and hypoxia; SuHypoxia) and cultured primary human cardiac and pulmonary artery adventitial fibroblasts to evaluate the relationship of TG2 to the processes of fibrosis, protein crosslinking, extracellular matrix collagen accumulation and fibroblast to myofibroblast transformation. Read More

    X-ray based lung function measurement reveals persistent loss of lung tissue elasticity in mice recovered from allergic airway inflammation.
    Am J Physiol Lung Cell Mol Physiol 2017 Aug 3:ajplung.00136.2017. Epub 2017 Aug 3.
    Synchrotron Light Source 'Elettra' Trieste
    Chronic asthma patients experience difficulties even years after the inciting allergen. Although studies in small animal asthma models have enormously advanced progress in uncovering the mechanisms of inception and development of the disease, little is known about the processes involved in the persistence of asthma symptoms in the absence of allergen exposure. Long term asthma mouse models have so far been scarce or not been able to reproduce the findings in patients. Read More

    FGF9 prevents pleural fibrosis induced by intra-pleural adenovirus injection in mice.
    Am J Physiol Lung Cell Mol Physiol 2017 Jul 20:ajplung.00508.2016. Epub 2017 Jul 20.
    University Paris Diderot
    Fibroblast Growth Factor 9 (FGF9) is necessary for fetal lung development and is expressed by epithelium and mesothelium. We evaluated the role of FGF9 overexpression on adenoviral-induced pleural injury in vivo and determined the biological effects of FGF9 on mesothelial cells in vitro. We assessed the expression of FGF9 and FGF receptors by mesothelial cells in both Human and mouse lungs. Read More

    A new target for caffeine in the developing lung: endoplasmic reticulum stress?
    Am J Physiol Lung Cell Mol Physiol 2017 Jul 20:ajplung.00251.2017. Epub 2017 Jul 20.
    University of Giessen and Marburg Lung Center (UGMLC)
    The utility of caffeine to manage apnea of prematurity is widely accepted, however, much controversy surrounds the potential for caffeine to drive post-natal lung maturation in settings of arrested lung development. Many studies have reported pathways relevant to lung injury and lung development are modulated by caffeine in vitro and in vivo, leading to the application of caffeine in experimental animal models of bronchopulmonary dysplasia (BPD). These studies have generated exciting, but at times confusing data. Read More

    Lethal Avian Influenza A (H5N1) Virus Induces Ataxic Breathing in Mice with Apoptosis of Pre-Botzinger Complex Neurons Expressing Neurokinin 1 Receptor.
    Am J Physiol Lung Cell Mol Physiol 2017 Jul 20:ajplung.00145.2017. Epub 2017 Jul 20.
    Lovelace Respiratory Research Institute
    Background: Lethal influenza A (H5N1) induces respiratory failure in humans. Although it also causes death at 7 day postinfection (dpi) in mice, the development of the respiratory failure and the viral impact on pre-Botzinger complex (PBC) neurons expressing neurokinin 1 receptor (NK1R), the respiratory rhythm-generator, have not been explored.

    Methods: Body temperature, weight, ventilation, arterial blood pH and gases were measured at 0, 2, 4, and 6 dpi in control, lethal HK483 and non-lethal HK486 viral infected mice. Read More

    Distinct PKA regulatory subunits mediate PGE2 inhibition of TGFβ-1-stimulated collagen I translation and myofibroblast differentiation.
    Am J Physiol Lung Cell Mol Physiol 2017 Jul 20:ajplung.00131.2017. Epub 2017 Jul 20.
    University of Michigan Health System
    Prostaglandin E2 (PGE2), via cAMP signaling, inhibits a variety of fibroblast functions relevant to fibrogenesis. Among these are their translation of collagen I protein and their differentiation to myofibroblasts. PKA is central to these actions, with cAMP binding to regulatory (R) subunits leading to the release of catalytic subunits. Read More

    TGF-β inhibits alveolar protein transport by promoting shedding, regulated intramembrane proteolysis and transcriptional downregulation of megalin.
    Am J Physiol Lung Cell Mol Physiol 2017 Jul 13:ajplung.00569.2016. Epub 2017 Jul 13.
    Justus Liebig University, Universities of Giessen and Marburg Lung Center
    Disruption of the alveolar-capillary barrier is a hallmark of acute respiratory distress syndrome (ARDS) that leads to accumulation protein-rich edema in the alveolar space often resulting in comparable protein concentrations in alveolar edema and plasma and causing deleterious remodeling. Patients who survive ARDS have approximately three-times lower protein concentrations in the alveolar edema than non-survivors, thus, the ability to remove excess protein from the alveolar space may be critical for a positive outcome. We have recently shown that clearance of albumin from the alveolar space is mediated by megalin, a 600 kDa transmembrane endocytic receptor and member of the low-density lipoprotein receptor superfamily. Read More

    Importance of kynurenine in pulmonary hypertension.
    Am J Physiol Lung Cell Mol Physiol 2017 Jul 13:ajplung.00517.2016. Epub 2017 Jul 13.
    Ludwig Boltzmann Institute for Lung Vascular Research; Medical University of Graz.
    The tryptophan metabolite kynurenine is significantly increased in pulmonary arterial hyper-tension (PAH) patients, and it is a potent vasodilator of systemic arteries. Our aim was to in-vestigate the role of kynurenine in the pulmonary circulation. Serum tryptophan, kynurenine and kynurenic-acid levels were measured in 20 idiopathic PAH (IPAH) patients, 20 healthy controls and 20 patients with chronic lung disease or meta-bolic syndrome without-PH. Read More

    Macrolides protect against Pseudomonas aeruginosa infection via inhibition of inflammasomes.
    Am J Physiol Lung Cell Mol Physiol 2017 Jul 6:ajplung.00123.2017. Epub 2017 Jul 6.
    Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
    Background Macrolides antibiotics have been used effectively in many chronic diseases, especially with Pseudomonas aeruginosa (P. aeruginosa) infection. The mechanisms underlying the therapeutic effects of macrolides in these diseases remain poorly understood. Read More

    Role of LTBP-4 in alveolarization, angiogenesis and fibrosis in lungs.
    Am J Physiol Lung Cell Mol Physiol 2017 Jul 6:ajplung.00031.2017. Epub 2017 Jul 6.
    Medical Faculty / University of Cologne
    Deficiency of the extracellular matrix (ECM) protein latent transforming growth factor beta (TGFβ) binding protein 4 (LTBP-4) results in lack of intact elastic fibers, which leads to disturbed pulmonary development and lack of normal alveolarization in humans and mice. Formation of alveoli and alveolar septation in pulmonary development requires the concerted interaction of extracellular matrix proteins, growth factors like TGFβ, fibroblasts and myofibroblasts to promote elastogenesis as well as vascular formation in the alveolar septae. To investigate the role of LTBP-4 in this context, lungs of LTBP-4 deficient (Ltbp4-/-) mice were analyzed in close detail. Read More

    Effects of prostaglandin lipid mediators on agonist-induced lung endothelial permeability and inflammation.
    Am J Physiol Lung Cell Mol Physiol 2017 Jun 29:ajplung.00519.2016. Epub 2017 Jun 29.
    University of Maryland
    Prostaglandins (PG), the products of cyclooxygenase-mediated conversion of arachidonic acid, become upregulated in many situations including allergic response, inflammation, injury, and exhibit variety of biological activities. Previous studies described barrier-enhancing and anti-inflammatory effects of PGE2 and PGI2 on vascular endothelial cells (EC). Yet, the effects of other PG members on EC barrier and inflammatory activation have not been systematically analyzed. Read More

    Mitochondrial quality control in alveolar epithelial cells damaged by S. aureus pneumonia in mice.
    Am J Physiol Lung Cell Mol Physiol 2017 Jun 29:ajplung.00197.2017. Epub 2017 Jun 29.
    Duke University
    (242 words) Mitochondrial damage is often overlooked in acute lung injury (ALI), but most of the lung's physiological processes, such as airway tone, muco-ciliary clearance, Va/Q matching, and immune surveillance require aerobic energy provision. Because the cell's processes of mitochondrial quality control (QC) regulate the elimination and replacement of damaged mitochondria to support cell survival, we evaluated mitochondrial biogenesis and mitophagy in the alveolar region of mice in a validated S. aureus pneumonia model. Read More

    Arterial stiffness induces remodeling phenotypes in pulmonary artery smooth muscle cells via YAP/TAZ-mediated repression of cyclooxygenase-2.
    Am J Physiol Lung Cell Mol Physiol 2017 Sep 22;313(3):L628-L647. Epub 2017 Jun 22.
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts;
    Pulmonary arterial stiffness is an independent risk factor for mortality in pulmonary hypertension (PH) and plays a critical role in PH pathophysiology. Our laboratory has recently demonstrated arterial stiffening early in experimental PH, along with evidence for a mechanobiological feedback loop by which arterial stiffening promotes further cellular remodeling behaviors (Liu F, Haeger CM, Dieffenbach PB, Sicard D, Chrobak I, Coronata AM, Suárez Velandia MM, Vitali S, Colas RA, Norris PC, Marinković A, Liu X, Ma J, Rose CD, Lee SJ, Comhair SA, Erzurum SC, McDonald JD, Serhan CN, Walsh SR, Tschumperlin DJ, Fredenburgh LE. JCI Insight 1: e86987, 2016). Read More

    Transforming growth factor-β stimulates Smad1/5 signaling in pulmonary artery smooth muscle cells and fibroblasts of the newborn mouse through ALK1.
    Am J Physiol Lung Cell Mol Physiol 2017 Sep 22;313(3):L615-L627. Epub 2017 Jun 22.
    Cardiovascular Research Center of the General Medical Services, Massachusetts General Hospital, Boston, Massachusetts;
    The intracellular signaling mechanisms through which TGF-β regulates pulmonary development are incompletely understood. Canonical TGF-β signaling involves Smad2/3 phosphorylation, Smad2/3·Smad4 complex formation and nuclear localization, and gene regulation. Here, we show that physiologically relevant TGF-β1 levels also stimulate Smad1/5 phosphorylation, which is typically a mediator of bone morphogenetic protein (BMP) signaling, in mouse pup pulmonary artery smooth muscle cells (mPASMC) and lung fibroblasts and other interstitial lung cell lines. Read More

    Cigarette smoke disrupts monolayer integrity by altering epithelial cell-cell adhesion and cortical tension.
    Am J Physiol Lung Cell Mol Physiol 2017 Sep 22;313(3):L581-L591. Epub 2017 Jun 22.
    Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland;
    Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Cigarette smoke (CS) drives disease development and progression. The epithelial barrier is damaged by CS with increased monolayer permeability. Read More

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