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American Journal of Physiology. Lung Cellular and Molecular Physiology

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https://www.readbyqxmd.com/read/28818871/sexual-dimorphism-of-the-pulmonary-transcriptome-in-neonatal-hyperoxic-lung-injury-identification-of-angiogenesis-as-a-key-pathway
#1
Cristian Coarfa, Yuhao Zhang, Suman Maity, Dimuthu Perera, Weiwu Jiang, Lihua Wang, Xanthi Couroucli, Bhagavatula Moorthy, Krithika Lingappan
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. The reasons underlying sexually dimorphic outcomes in premature neonates are not known. We hypothesized that sex-specific modulation of biological processes in the lung under hyperoxic conditions, contributes to sex-based differences...
August 17, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28818870/fra-2-negatively-regulates-postnatal-alveolar-septation-by-modulating-myofibroblast-function
#2
Kazuyuki Tsujino, John T Li, Tatsuya Tsukui, Xin Ren, Latifa Bakiri, Erwin F Wagner, Dean Sheppard
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...
August 17, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28798259/endothelial-cell-related-autophagic-pathways-in-sugen-hypoxia-exposed-pulmonary-arterial-hypertensive-rats
#3
Fumiaki Kato, Seiichiro Sakao, Takao Takeuchi, Toshio Suzuki, Rintaro Nishimura, Tadashi Yasuda, Nobuhiro Tanabe, Koichiro Tatsumi
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...
August 10, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28798258/preserved-right-ventricular-integrity-in-a-new-telemetric-rat-model-of-severe-pulmonary-hypertension
#4
Catharina Schreiber, Magdalena S Eilenberg, Attila Kiss, Helga Bergmeister, Bruno K Podesser, Julia Mascherbauer, Diana Bonderman
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. To overcome shortcomings of standard hemodynamic assessment, we modified an established rat model, where severe PAH is induced by left-sided pneumonectomy plus monocrotaline injection...
August 10, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28798257/aquaporin-1-mediated-changes-in-pulmonary-arterial-smooth-muscle-cell-migration-and-proliferation-involve-%C3%AE-catenin
#5
Xin Yun, Haiyang Jiang, Ning Lai, Jian Wang, Larissa A Shimoda
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.e., c-Myc and cyclin D1) related to cell migration and proliferation...
August 10, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28798256/metabolic-characterization-and-rna-profiling-reveal-glycolytic-dependence-of-pro-fibrotic-phenotype-of-alveolar-macrophages-in-lung-fibrosis
#6
Na Xie, Huachun Cui, Jing Ge, Sami Banerjee, Sijia Guo, Shubham Dubey, Edward Abraham, Rui-Ming Liu, Gang Liu
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. Furthermore, main metabolic programs and their regulation of cellular phenotype are completely unknown. In this study, we comprehensively analyzed the expression profile and main metabolic programs in alveolar macrophages from mice with or without experimental pulmonary fibrosis...
August 10, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28798255/benefits-of-oxytocin-administration-in-obstructive-sleep-apnea
#7
Vivek Jain, Joseph Marbach, Shawn Kimbro, David C Andrade, Arad Jain, Eleanor Capozzi, Kyle Mele, Rodrigo Del Rio, Matthew W Kay, David Mendelowitz
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.u.). Changes in cardiorespiratory events during sleep, including apnea and hypopnea durations and frequency, risk of event-associated arousals, and heart rate variability were assessed. Oxytocin significantly increased indices of parasympathetic activity, including heart rate variability, total sleep time, and the Post-Polysommogram Sleep Assessment (PPSA) score, an index of self-reported sleep satisfaction...
August 10, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28798254/oxygen-dependent-changes-in-lung-development-do-not-affect-epithelial-infection-with-influenza-a-virus
#8
William Domm, Min Yee, Ravi S Misra, Robert Gelein, Aitor Nogales, Luis Martinez Sobrido, Michael A O'Reilly
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...
August 10, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28798253/cyp2e1-regulates-the-development-of-radiation-induced-pulmonary-fibrosis-via-er-stress-and-ros-dependent-mechanisms
#9
Beomseok Son, TaeWoo Kwon, Sungmin Lee, IkJoon Han, Wanyeon Kim, HyeSook Youn, BuHyun Youn
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. 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...
August 10, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28798252/pollen-induced-oxidative-dna-damage-response-regulates-mirnas-controlling-allergic-inflammation
#10
Leopoldo Aguilera-Aguirre, Wenjing Hao, Lang Pan, Xiaoxue Li, Alfredo Saavedra-Molina, Attila Bacsi, Zsolt Radak, Sanjiv Sur, Allan R Brasier, Xueqing Ba, Istvan Boldogh
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). OGG1 in complex with 8-oxoG acts as a GDP-GTP exchange factor and induces acute inflammation; however, the mechanism(s) by which OGG1 signaling regulates allergic airway inflammation is not known...
August 10, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28798251/lungmap-the-molecular-atlas-of-lung-development-program
#11
Maryanne E Ardini-Poleske, Robert Fred Clark, Charles Ansong, James P Carson, Richard A Corley, Gail H Deutsch, James S Hagood, Naftali Kaminski, Thomas J Mariani, Steven S Potter, Gloria S Pryhuber, David Warburton, Jeffrey A Whitsett, Scott M Palmer, Namasivayam Ambalavanan, The LungMAP Consortium
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...
August 10, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28775099/alternative-pre-mrna-splicing-of-toll-like-receptor-signaling-components-in-peripheral-blood-mononuclear-cells-from-ards-patients
#12
Rachel Z Blumhagen, Brenna R Hedin, Kenneth C Malcolm, Ellen L Burnham, Marc Moss, Edward Abraham, Tristan J Huie, Jerry A Nick, Tasha E Fingerlin, Scott Alper
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...
August 3, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28775098/influenza-virus-infection-alters-ion-channel-function-of-airway-and-alveolar-cells-mechanisms-and-physiological-sequelae
#13
James D Londino, Ahmed Lazrak, James F Collawn, Zsuzsanna Bebok, Kevin S Harrod, Sadis Matalon
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...
August 3, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28775097/platelet-derived-growth-factor-receptor-alpha-pdgfr%C3%AE-and-ras-related-c3-botulinum-toxin-substrate-1-rac1-regulate-mechano-responsiveness-of-lung-fibroblasts
#14
Stephen E McGowan, Diann M McCoy
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. PDGFRα-expressing, αSMA-containing, alveolar cells re-distribute in the elongating septum, suggesting that they migrate to the alveolar entry rings where mechanical tension is higher...
August 3, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28775096/repetitive-intradermal-bleomycin-injections-evokes-t-helper-cell-2-cytokine-driven-pulmonary-fibrosis
#15
Brijendra Singh, Rajesh K Kasam, Vishwaraj Sontake, Thomas A Wynn, Satish K Madala
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...
August 3, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28775095/transglutaminase-2-in-pulmonary-and-cardiac-tissue-remodeling-in-experimental-pulmonary-hypertension
#16
Krishna C Penumatsa, Deniz Toksoz, Rod R Warburton, Mousa Kharnaf, Ioana R Preston, Navin Kumar Kapur, Chaitan Khosla, Nicholas S Hill, Barry L Fanburg
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...
August 3, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28775094/x-ray-based-lung-function-measurement-reveals-persistent-loss-of-lung-tissue-elasticity-in-mice-recovered-from-allergic-airway-inflammation
#17
Marietta Andrea Markus, Sergej Borowik, Marius Reichardt, Giuliana Tromba, Frauke Alves, Christian Dullin
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. Here we used a common ovalbumin induced acute allergic airway inflammation mouse model to study lung function and remodeling after a four months recovery period...
August 3, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28729349/fgf9-prevents-pleural-fibrosis-induced-by-intra-pleural-adenovirus-injection-in-mice
#18
Aurélien Justet, Audrey Joannes, Valérie Besnard, Joëlle Marchal-Sommé, Madeleine Jaillet, Phillippe Bonniaud, Jean-Michel Sallenave, Brigitte Solhonne, Yves Castier, Pierre Mordant, Hervé Mal, Aurélie Cazes, Raphael Borie, Arnaud A Mailleux, Bruno Crestani
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. Intrapleural injection of an adenovirus expressing human FGF9 (AdFGF9) or a control adenovirus (Adcont) was performed...
July 20, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28729348/a-new-target-for-caffeine-in-the-developing-lung-endoplasmic-reticulum-stress
#19
Philipp Rath, Claudio Nardiello, Rory E Morty
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...
July 20, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28729347/lethal-avian-influenza-a-h5n1-virus-induces-ataxic-breathing-in-mice-with-apoptosis-of-pre-botzinger-complex-neurons-expressing-neurokinin-1-receptor
#20
Jianguo Zhuang, Na Zang, Chunyan Ye, Fadi Xu
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...
July 20, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
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