American Journal of Respiratory Cell and Molecular Biology最新文献

{"title":"The interplay of airway epithelium and biomechanical stress in pulmonary fibrosis.","authors":"Liqin Lin, Johad Khoury, Guojun Zhang, Jason Szafron, Edward P Manning, Farida Ahangari","doi":"10.1093/ajrcmb/aanag066","DOIUrl":"10.1093/ajrcmb/aanag066","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is a progressive and often fatal lung disease characterized by the scarring and stiffening of lung tissue. While its exact cause remains elusive, emerging evidence underscores the significant role of mechanical forces and aberrant epithelial responses in its pathogenesis. The airway epithelium serves as a critical barrier and regulator of lung function, exhibiting abnormal responses to mechanical stress. Recent studies suggest that the abnormal airway epithelial response to mechanical stressors contributes to the progression of IPF and serves as an early indicator of disease onset. Understanding the complex interplay between mechanical forces and these cells in IPF not only sheds light on disease mechanisms but also opens avenues for novel therapeutic interventions targeting these pathways. The goal of this review is to highlight the most recent advances in understanding mechanobiology and the interaction between biomechanical properties and the airway epithelium in the pathogenesis of IPF. We seek to describe a positive feedback loop underlying pulmonary fibrosis, in which pro-fibrotic mechanobiological responses of airway epithelial cells drive biomechanical alterations in the lung airways. In parallel, these biomechanical changes further stimulate pro-fibrotic responses in the epithelial cells, perpetuating the cycle. Additionally, we aim to provide a comprehensive perspective on the role of lung biomechanics in the progression of fibrosis, emphasizing the critical need to disrupt this insidious feedback loop to halt or prevent the advancement of lung fibrosis.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"1016-1031"},"PeriodicalIF":5.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel role of von Willebrand factor-αvβ3 integrin in human pulmonary artery smooth muscle cell.","authors":"Sara Abd Al Rahim, Bruno Ribeiro Baptista, Huguette Louis, Cécile V Denis, Christophe Guignabert, Ly Tu, Véronique Regnault, Patrick Lacolley, Julien Perrin, Ari Chaouat","doi":"10.1093/ajrcmb/aanag083","DOIUrl":"10.1093/ajrcmb/aanag083","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"1146-1148"},"PeriodicalIF":5.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pure isolation, culture, and postinjury lineage tracing of mouse visceral pleural mesothelial cells.","authors":"Akikazu Endo, Yasunori Enomoto, Ryo Horiguchi, Shiori Meguro, Hideya Kawasaki, Isao Kosugi, Kenta Iijima, Shuji Takabayashi, Satoshi Baba, Toshihide Iwashita","doi":"10.1093/ajrcmb/aanaf002","DOIUrl":"10.1093/ajrcmb/aanaf002","url":null,"abstract":"<p><p>Pleural mesothelial cells (PMCs) are a major component of the pleura. The involvement of visceral PMCs has been suggested in several pleural or subpleural lung diseases, thus highlighting the importance of animal experiments using these cells. However, in wild-type rodent lungs, no direct and pure isolation method for visceral PMCs has been established so far. Using reanalyzed single-cell RNA sequencing data, we identified that mesothelin (Msln), a specifically expressed gene in visceral PMCs, can be useful for live cell sorting. After collecting cells by scraping the visceral pleura, MSLN+EpCAM-CD45-CD31-PDGFRα-CD146- cells with large size (≥1.4 times the median value of forward scatter in total cells) mostly exhibited WT1 protein (WT1 positivity in immunocytochemistry: 93.3% ± 0.8%). The sorted PMCs were culturable, and they responded generally predictably to several growth factors and cytokines, including genetic changes suggestive of a TGF-β-induced mesothelial-to-mesenchymal transition. In vivo experiments performed using PMC-specific reporter mice (Wt1-creERT2; tdTomato) demonstrated that intrapleural administration of bleomycin with carbon induced proliferation of PMCs in the visceral pleura. Importantly, some PMC-derived cells differentiated into α-smooth muscle actin-positive myofibroblasts with decreased MSLN expression, indicating that our method using MSLN is suitable only for uninjured lungs. In summary, we propose a novel and qualified method for visceral PMC isolation, which will aid in the elucidation of the mechanisms underlying pleura-related human lung diseases.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"1009-1015"},"PeriodicalIF":5.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13424672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147281792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Managing the stress: taurine supplementation in bronchopulmonary dysplasia.","authors":"Thomas J Lynch, Rodney D Britt","doi":"10.1093/ajrcmb/aanag056","DOIUrl":"10.1093/ajrcmb/aanag056","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"984-985"},"PeriodicalIF":5.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lung-protective and neurotoxic: the double-edged sword of tau in respiratory infections.","authors":"Ajay Keerthy, Joseph A Hippensteel","doi":"10.1093/ajrcmb/aanag084","DOIUrl":"10.1093/ajrcmb/aanag084","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"994-996"},"PeriodicalIF":5.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nintedanib increases BCL-2 in fibrotic fibroblasts, enhancing ABT-199 apoptosis and fibrosis resolution.","authors":"Joseph C Cooley, Sarah K Penick, Jasmine A Wilson, Nomin Javkhlan, Daniel G Foster, Benjamin L Edelman, Cody A Schott, Stephen M Humphries, David A Lynch, David A Schwartz, David W H Riches, Elizabeth F Redente","doi":"10.1093/ajrcmb/aanag045","DOIUrl":"10.1093/ajrcmb/aanag045","url":null,"abstract":"<p><strong>Rationale: </strong>Progressive fibrosing interstitial lung diseases (PF-ILDs) have a large global impact and there is a pressing need to develop new therapies.</p><p><strong>Objectives: </strong>We investigate if nintedanib augments apoptosis of profibrotic fibroblasts induced by BCL-2 inhibition with ABT-199, and if combination therapy reverses pulmonary fibrosis.</p><p><strong>Methods: </strong>Healthy and PF-ILD fibroblasts were treated with nintedanib, and BCL-2 family member expression was measured. Fibroblasts and precision-cut lung slices were analyzed for apoptosis after ABT-199 and nintedanib treatment. Therapeutic interventions with ABT-199 and nintedanib in mice with repetitive bleomycin-induced progressive pulmonary fibrosis were assessed for profibrotic fibroblast and aberrant transitional epithelial cell apoptosis, lung collagen content, longitudinal oxygen saturation, and micro-computed tomography disease burden.</p><p><strong>Measurements and main results: </strong>Nintedanib treatment increased expression of proapoptotic BIM and antiapoptotic BCL-2 in PF-ILD primary fibroblasts. There was significantly increased apoptosis of fibroblasts in vitro after ABT-199. This was augmented after nintedanib co-treatment both in PF-ILD fibroblasts and precision-cut lung slices. ABT-199 significantly improved fibrosis in mice, which was further enhanced after nintedanib co-treatment, by targeted apoptosis of pathogenic fibroblasts and transitional epithelial cells.</p><p><strong>Conclusions: </strong>The proapoptotic effects of ABT-199 were increased with nintedanib co-treatment and reversed fibrosis in mice. Combination treatment induced profibrotic fibroblast and aberrant transitional epithelial cell apoptosis. These studies highlight a new mechanistic strategy to treat PF-ILD.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"1103-1113"},"PeriodicalIF":5.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13424840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond slowing decline: leveraging apoptotic synergy to reverse pulmonary fibrosis.","authors":"Yohannes A Mebratu, Jeffrey C Horowitz","doi":"10.1093/ajrcmb/aanag105","DOIUrl":"10.1093/ajrcmb/aanag105","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"988-990"},"PeriodicalIF":5.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13424674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147873047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired taurine transport contributes to bronchopulmonary dysplasia: a systems biology analysis.","authors":"Xigang Jing, Yekai Wang, Mark Roethle, Shuang Jia, Michelle Teng, Girija G Konduri, Martin J Hessner, Kirkwood A Pritchard, Billy W Day, Yan Jin, Xiaolong Ma, Stephen Naylor, Chien-Wei Lin, Haiwei Gu, Jianhai Du, Ru-Jeng Teng","doi":"10.1093/ajrcmb/aanag033","DOIUrl":"10.1093/ajrcmb/aanag033","url":null,"abstract":"<p><p>Metabolic dysregulation is implicated in the development of bronchopulmonary dysplasia (BPD). Taurine is an essential amino acid and a critical molecule in oxidative phosphorylation that mechanistically modulates angiogenesis. Using a neonatal hyperoxia model supported by metabolomic and single-cell RNA-seq analyses, we showed that insufficient taurine contributes to alveolar simplification in BPD. To model BPD, Sprague-Dawley rat pups were exposed to >90% oxygen. Plasma and lungs were obtained for multiomics. Pups received tunicamycin or tauroursodeoxycholic acid to study mechanisms that modulate taurine metabolism. Taurine was administered as rescue therapy after identifying its depletion in the BPD lungs. Genes and proteins of oxidative phosphorylation were enriched in BPD lungs, whereas complex I (C-I) activity was paradoxically decreased. The reduction of taurine and taurine-dependent C-I core subunits, NADH Dehydrogenase Subunits 5 and 6 (ND5, ND6), in BPD lungs explains this C-I paradox. The accompanying increase of plasma taurine in BPD pups indicates a decreased taurine transport, which can be explained by the reduced glycosylation and increased degradation of the taurine transporter. The results of complementary treatments with tunicamycin and tauroursodeoxycholic acid, indicate that endoplasmic reticulum stress contributes to impaired taurine transport in BPD rat lungs. Taurine treatment increased the expression of ND5 and ND6, the percentage of proliferating general capillary endothelial cells, and alveolar complexity in BPD lungs. Our multiomic approach reveals that taurine enhances endothelial resilience by activating the unfolded protein response, and might clinically benefit premature lungs. This represents a distinct antioxidant mechanism not previously characterized in hyperoxic lung injury.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"1058-1072"},"PeriodicalIF":5.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147281754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Infants who develop bronchopulmonary dysplasia have an airway endotype defined by vimentin expression and ciliary loss.","authors":"Laurie C Eldredge, Yan Han, Gail H Deutsch, Jennifer M S Sucre, Shawyon P Shirazi, Caroline Stefani, Stephan Pribitzer, Stephen R Reeves, Lucille M Rich, Elizabeth R Vanderwall, Steven F Ziegler, Jason S Debley","doi":"10.1093/ajrcmb/aanag044","DOIUrl":"10.1093/ajrcmb/aanag044","url":null,"abstract":"<p><strong>Rationale: </strong>Bronchopulmonary dysplasia (BPD) arises from disrupted lung development after preterm birth and produces structural deficits at every level of the respiratory tree. Lower airway disease is emerging as a clinically significant BPD phenotype with increased mortality, yet the molecular mechanisms whereby preterm birth disrupts airway development remain poorly defined.</p><p><strong>Objectives: </strong>To develop a human model of lower airway disease following preterm birth and to define a molecular endotype of evolving BPD (eBPD) at baseline and in response to injury.</p><p><strong>Methods: </strong>An ex vivo organotypic airway epithelial cell (AEC) model was combined with well-characterized pathologic and transcriptomic patient samples for quantitative immunohistochemistry and RNA-sequencing analyses.</p><p><strong>Measurements and main results: </strong>Compared to AECs from healthy controls, eBPD-derived AECs exhibited reduced proliferation, impaired differentiation to ciliated epithelium, and expansion of a vimentin-positive population with a transcriptional profile associated with impaired AEC differentiation. Following hyperoxia exposure, eBPD-derived AECs mounted a robust vimentin response ex vivo, paralleling increased vimentin expression observed in airway cells from lung tissue of human infants with BPD.</p><p><strong>Conclusions: </strong>Using an organotypic model of neonatal airway differentiation, we demonstrate eBPD is associated with impaired AEC differentiation, increased vimentin-expression and concomitant loss of ciliated cells, and an exaggerated vimentin response to hyperoxic injury. These findings mimic the effects of prematurity in airway cells in human patients. These data support a mechanism whereby hyperoxia leads to impaired epithelial differentiation and associated lower airway dysfunction in BPD and inform future mechanistic studies interrogating the role of intermediate filaments in maladaptive epithelial repair.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"1044-1057"},"PeriodicalIF":5.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13424598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"zDHHC21 loss of function activates lung fibroblasts by regulating PTEN palmitoylation.","authors":"Bieerkehazhi Shayahati, Aaron K McDowell-Sanchez, Askar M Akimzhanov, Konstantin Tsoyi","doi":"10.1093/ajrcmb/aanag097","DOIUrl":"10.1093/ajrcmb/aanag097","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"1142-1145"},"PeriodicalIF":5.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13424684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147961995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}