American Journal of Physiology. Lung Cellular and Molecular Physiology This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

Sphingosine kinase 1 specific inhibitor PF543 reduces goblet cell metaplasia of bronchial epithelium in an acute asthma model
Am J Physiol Lung Cell Mol Physiol. 2024 Jan 30. doi: 10.1152/ajplung.00269.2023. Online ahead of print.ABSTRACTSphingosine kinase 1 (SPHK1) has been shown to play a key role in the pathogenesis of asthma where SPHK1 generated S1P is known to mediate innate and adaptive immunity while promoting mast cell degranulation. Goblet cell metaplasia (GCM) contributes to airway obstruction in asthma and has been demonstrated in animal models. We investigated the role of PF543, a SPHK1 specific inhibitor, in preventing the pathogenesis of GCM using a murine (C57BL/6) model of allergen-induced acute asthma. Treatment with PF543 prior...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - January 30, 2024 Category: Cytology Authors: Tara Sudhadevi Steven J Ackerman Anjum Jafri Prathima Basa Alison W Ha Viswanathan Natarajan Anantha Harijith Source Type: research

Quantification of smooth muscle in human airways by polarization-sensitive optical coherence tomography requires correction for perichondrium
We report the use of whole fresh human and pig airways to perform a detailed side-by-side qualitative and quantitative validation of PS-OCT against gold standard histology. We matched and quantified 120 sections from five human and seven pig (small and large) airways and linked PS-OCT signatures of ASM to the tissue structural appearance in histology. Notably, we found that human cartilage perichondrium can share with ASM the properties of birefringence and circumferential alignment of fibers, making it a significant confounder for ASM detection. Measurements not corrected for perichondrium overestimated ASM content severa...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - January 23, 2024 Category: Cytology Authors: Michael J Hackmann Alvenia Cairncross John G Elliot Siobhain Mulrennan Kris Nilsen Bruce R Thompson Qingyun Li Karol Karnowski David D Sampson Robert A McLaughlin Barry Cense Alan L James Peter B Noble Source Type: research

< em > In utero < /em > ventilation induces lung parenchymal and vascular alterations in extremely preterm fetal sheep
Am J Physiol Lung Cell Mol Physiol. 2024 Jan 22. doi: 10.1152/ajplung.00249.2023. Online ahead of print.ABSTRACTExtremely preterm infants are often exposed to long durations of mechanical ventilation to facilitate gas exchange, resulting in ventilation-induced lung injury (VILI). New lung protective strategies utilising non-invasive ventilation or low tidal volumes are now common but have not reduced rates of bronchopulmonary dysplasia. We aimed to determine the effect of 24 hours of low tidal volume ventilation on the immature lung by ventilating preterm fetal sheep in utero. Preterm fetal sheep at 110 ± 1(SD) days gesta...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - January 22, 2024 Category: Cytology Authors: Zahrah Azman Kayla Vidinopoulos Ainsley Somers Stuart B Hooper Valerie A Zahra Alison Thiel Robert Galinsky Nhi T Tran Beth J Allison Graeme R Polglase Source Type: research

Two pore potassium channel trek-1 (k2p2.1) regulates nlrp3 inflammasome activity in macrophages
Am J Physiol Lung Cell Mol Physiol. 2024 Jan 22. doi: 10.1152/ajplung.00313.2023. Online ahead of print.ABSTRACTBecause of the importance of potassium efflux in inflammasome activation, we investigated the role of the two-pore potassium (K2P) channel TREK-1 in macrophage inflammasome activity. Using primary alveolar macrophages (AMs) and bone marrow derived macrophages (BMDMs) from wild type (wt) and TREK-1-/- mice, we measured responses to inflammasome priming (using LPS) and activation (LPS +ATP). We measured IL-1β, caspase-1, and NLRP3 via ELISA and western blot. A membrane-permeable potassium indicator was used to mea...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - January 22, 2024 Category: Cytology Authors: Camille N Immanuel Bin Teng Brittany E Dong Elizabeth M Gordon Charlean Luellen Benjamin Lopez Jeffrey Harding Stephania A Cormier Elizabeth A Fitzpatrick Andreas Schwingshackl Christopher M Waters Source Type: research

Brg1/PRMT5 Nuclear Complex Epigenetically Regulates FOXO1 In IPF Mesenchymal Progenitor Cells
Am J Physiol Lung Cell Mol Physiol. 2024 Jan 22. doi: 10.1152/ajplung.00248.2023. Online ahead of print.ABSTRACTWe have discovered intrinsically fibrogenic mesenchymal progenitor cells (MPCs) in the human IPF lung. IPF MPCs display a durably distinct transcriptome suggesting that they have undergone epigenetic modifications. Prior studies indicate that the chromatin remodeler Brg1 associates with the arginine methyltransferase PRMT5 to epigenetically regulate transcription factors. We hypothesize that a Brg1/PRMT5 nuclear complex epigenetically regulates critical nodes in IPF MPC self-renewal signaling networks. IPF and co...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - January 22, 2024 Category: Cytology Authors: Aiham H Jbeli Libang Yang Hong Xia Adam J Gilbertsen Peter B Bitterman Craig A Henke Source Type: research

Role of ZIP kinase in development of myofibroblast differentiation from HPMCs
Am J Physiol Lung Cell Mol Physiol. 2024 Jan 22. doi: 10.1152/ajplung.00251.2023. Online ahead of print.ABSTRACTDuring the development of pleural fibrosis, pleural mesothelial cells (PMCs) undergo phenotypic switching from differentiated mesothelial cells to mesenchymal cells (MesoMT). Here, we investigated how external stimuli such as TGF-β induce HPMC-derived myofibroblast differentiation to facilitate the development of pleural fibrosis. TGF- significantly increased di-phosphorylation but not mono-phosphorylation of myosin II regulatory light chain (RLC) in HPMCs. An increase in RLC di-phosphorylation was also found...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - January 22, 2024 Category: Cytology Authors: Young-Yeon Choo Tsuyoshi Sakai Reiko Ikebe Ann Jeffers Steven Idell Torry A Tucker Mitsuo Ikebe Source Type: research

A gel-coated air-liquid-interface culture system with tunable substrate stiffness matching healthy and diseased lung tissues
Am J Physiol Lung Cell Mol Physiol. 2024 Jan 22. doi: 10.1152/ajplung.00153.2023. Online ahead of print.ABSTRACTSince its invention in the late 1980s, the air-liquid-interface (ALI) culture system has been the standard in vitro model for studying human airway biology and pulmonary diseases. However, in a conventional ALI system, cells are cultured on a porous plastic membrane that is much stiffer than human airway tissues. Here, we develop a gel-ALI culture system by simply coating the plastic membrane with a thin layer of hydrogel with tunable stiffness matching that of healthy and fibrotic airway tissues. We determine th...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - January 22, 2024 Category: Cytology Authors: Zhijian He Catherine Chu Riley Dickson Kenichi Okuda Liheng Cai Source Type: research

Fatty acid metabolism promotes TRPV4 activity in lung microvascular endothelial cells in pulmonary arterial hypertension
In this study, using human data, serum samples from SuHx rats, and SuHx-MVECs, we describe the consequences of increased MVEC fatty acid oxidation in PAH. In human samples, we observed an increase in long-chain fatty acid levels that was associated with PAH severity. Next, using SuHx rats and SuHx-MVECs, we observed increased intracellular levels of lipids. We also show that increasing intracellular lipid content increases TRPV4 activity, whereas inhibiting fatty acid oxidation normalizes basal calcium levels in SuHx-MVECs. By exploring the fate of fatty acid-derived carbons, we observed that the metabolite linking increas...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - January 16, 2024 Category: Cytology Authors: Nicolas Philip Xin Yun Hongyang Pi Samuel Murray Zack Hill Jay Fonticella Preston Perez Cissy Zhang Wimal Pathmasiri Susan Sumner Laura Servinsky Haiyang Jiang John C Huetsch William M Oldham Scott Visovatti Peter J Leary Sina A Gharib Evan Brittain Cathe Source Type: research

Circulating Biomarker Analyses in a Longitudinal Cohort of Patients with IPF
In this study, we asked whether levels of select circulating biomarkers in patients with IPF demonstrated changes in response to treatment over time, and whether treatment with pirfenidone and nintedanib led to differential biomarker expression. Serial plasma samples from 48 IPF patients on usual treatment and 6 healthy volunteers were analyzed to identify differentially expressed blood protein. Hypothesis-driven potential biomarker selection was based on recent literature, internal preclinical data, and the PROLIFIC Consortium (1) proposed biomarkers of pulmonary fibrosis. We compared our findings to public databases to p...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - January 16, 2024 Category: Cytology Authors: Christina Ebert Alice M Walsh Larisa Sereda Carole Wilson Peter H Schafer Aryeh Fischer Lei Zhao Francisco Ramirez-Valle David Gordon Lynn M Schnapp Source Type: research

Small airway fibroblasts from Chronic Obstructive Pulmonary Disease patients exhibit cellular senescence
CONCLUSIONS: These data suggest COPD SAF are senescent and may be associated with fibrotic properties and mitochondrial dysfunction. Further understanding cellular senescence in SAF may lead to potential therapies to limit SAD progression.PMID:38150543 | DOI:10.1152/ajplung.00419.2022 (Source: American Journal of Physiology. Lung Cellular and Molecular Physiology)
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - December 27, 2023 Category: Cytology Authors: Catherine L Wrench Jonathan R Baker Sue Monkley Peter S Fenwick Lynne Murray Louise E Donnelly Peter J Barnes Source Type: research

Viral airway injury promotes cell engraftment in an in vitro model of cystic fibrosis cell therapy
We examined competition dynamics by time-lapse confocal imaging and found that delivered cells accelerate airway regeneration by incorporating into the epithelium. Irradiating the repairing epithelium granted engrafting cells a competitive advantage by diminishing resident stem cell proliferation. Intentionally, causing severe injury to the lungs of people with CF would be dangerous. However, naturally occurring events like viral infection can induce similar epithelial damage with patches of denuded epithelium. We found that viral preconditioning promoted effective engraftment of cells primed for viral resistance.NEW &...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - December 27, 2023 Category: Cytology Authors: Rhianna E Lee Teresa M Mascenik Sidra C Major Jacob R Galiger Emily Bulik-Sullivan Priscila F Siesser Catherine A Lewis James E Bear Jake A Le Suer Finn J Hawkins Raymond J Pickles Scott H Randell Source Type: research

Hemopexin Reverses Activation of Lung eIF2a and Decreases Mitochondrial Injury in Chlorine Exposed Mice
Am J Physiol Lung Cell Mol Physiol. 2023 Dec 27. doi: 10.1152/ajplung.00273.2023. Online ahead of print.ABSTRACTWe assessed the mechanisms by which non-encapsulated heme, released in the plasma of mice post exposure to chlorine (Cl2) gas, resulted in the initiation and propagation of acute lung injury. We exposed adult male and female C57BL/6 mice to Cl2 (500 ppm for 30 min), returned them to room air, and injected them intramuscularly with either human hemopexin (hHPX; 5 µg/ g BW in 50 µl saline) or vehicle at 1h post exposure. Upon return to room air, Cl2 exposed mice, injected with vehicle, developed respiratory acido...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - December 27, 2023 Category: Cytology Authors: Sadis Matalon Zhihong Yu Shubham Dubey Israr Ahmad Emily M Stephens Ammar Saadoon Alishlash Ashley Meyers Douglas Cossar Donald Stewart Edward P Acosta Kyoko Kojima Tamas Jilling James A Mobley Source Type: research

Viral Airway Injury Promotes Cell Engraftment in an In Vitro Model of Cystic Fibrosis Cell Therapy
We examined competition dynamics by time-lapse confocal imaging and found that delivered cells accelerate airway regeneration by incorporating into the epithelium. Irradiating the repairing epithelium granted engrafting cells a competitive advantage by diminishing resident stem cell proliferation. Intentionally causing severe injury to the lungs of people with CF would be dangerous. However, naturally occurring events like viral infection can induce similar epithelial damage with patches of denuded epithelium. We found that viral preconditioning promoted effective engraftment of cells primed for viral resistance.PMID:38150...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - December 27, 2023 Category: Cytology Authors: Rhianna E Lee Teresa M Mascenik Sidra C Major Jacob R Galiger Emily Bulik-Sullivan Priscila F Siesser Catherine A Lewis James E Bear Jake A Le Suer Finn J Hawkins Raymond J Pickles Scott H Randell Source Type: research