American Journal of Respiratory Cell and Molecular Biology最新文献

{"title":"Casein Kinase 1 Delta (CK1δ) Is Implicated in TGF-β1 Activation of Human Lung Myofibroblasts.","authors":"Meina Li, Stephanie S Zhang, Trudi Harris, Qianyu Chen, Alastair G Stewart","doi":"10.1165/rcmb.2024-0421LE","DOIUrl":"https://doi.org/10.1165/rcmb.2024-0421LE","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952700","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":"Matrix Softness Induces an Afibrogenic Lipofibroblast Phenotype in Fibroblasts from IPF Patients.","authors":"Asres Berhan, Avanka Gunatilaka, Chiaohwei Lee, Stephanie Zhang, Daniel Tan, Trudi Harris, Jade Jaffar, Fernando Jativa, Ingrid Lönnstedt, Monther Alhamdoosh, Milica Ng, Shenna Langenbach, Swati Varshney, Nicholas A Williamson, Peter V S Lee, Nick Wilson, Bryan Gao, Glen Westall, Alastair G Stewart","doi":"10.1165/rcmb.2025-0030OC","DOIUrl":"https://doi.org/10.1165/rcmb.2025-0030OC","url":null,"abstract":"<p><p>Contractile myofibroblasts immersed in stiffened remodelled extracellular matrix (ECM) characterise fibrotic lesions in idiopathic pulmonary fibrosis (IPF). Lipofibroblasts are lipid-droplet containing interstitial fibroblasts that support functional homeostasis of the developing and adult lung. We show that stiff substrates augment myofibroblast differentiation and ECM production <i>in vitro</i> under basal conditions and following transforming growth factor-β1 (TGF-β1) incubation when cultured on tissue culture plastic, whereas culture in soft microenvironments (as spheroids or on soft collagen-coated substrate) redirects myofibroblast to a lipofibroblast-like phenotype (identified by expression of adipose differentiation-related protein (ADRP) and intracellular lipid droplets), with reduced basal alpha-smooth muscle actin (α-SMA), collagen I, vimentin (VIM) and fibronectin (FN1) expression. The fibrogenic effects of TGF-β1 are prevented in fibroblasts cultured in soft settings. Global proteomics showed similar numbers of TGF-β1-induced differentially expressed proteins in stiff and soft settings (271 and 436, respectively). Of these, only 33 were similarly altered by TGF-β1; 200 were exclusively altered by TGF-β1 in stiff setting; 365 in soft setting, while 38 showed opposite responses. Reductions in YAP/TAZ, beta-catenin and SMAD expression and their limited nuclear levels in soft settings may explain the \"afibrogenic\" characteristic of these lipofibroblasts. Thus, in spheroids of lipofibroblasts TGF-β1 intracellular signalling is redirected and uncoupled from fibrogenesis, including YAP/TAZ, β-catenin and SMAD. Understanding the proximal causal mechano-transduction signalling networks that are differentially active in soft and stiff microenvironments may reveal novel drug targets for fibrosis treatment.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961955","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":"VEGF-D Protects the Lung in Neonatal Hyperoxia-induced Lung Injury.","authors":"Lakshanie C Wickramasinghe, Elan L'Estrange-Stranieri, Bailey Cardwell, Caitlin A O'Brien, Ali Shad, Amy T Hsu, Peter van Wijngaarden, Gary P Anderson, Steven A Stacker, Marc G Achen, Evelyn Tsantikos, Margaret L Hibbs","doi":"10.1165/rcmb.2024-0544OC","DOIUrl":"https://doi.org/10.1165/rcmb.2024-0544OC","url":null,"abstract":"<p><p>Bronchopulmonary dysplasia (BPD) is a serious lung disease that affects premature infants born with developmentally immature lungs. Supplemental oxygen, while a lifesaving treatment, provokes inflammation and oxidative stress causing microvasculature injury, pulmonary edema and abnormal lung development. Impaired pulmonary vascular development is implicated in BPD; however, the role of the lymphatics is poorly understood. Studies utilized an established animal model, where mice were exposed on day of birth for 14 days to 75% oxygen to induce hallmark features of BPD including pulmonary edema. Single cell RNA sequencing data was analysed to examine vascular endothelial growth factor-D (VEGF-D) expression in the neonatal lung and to define how fibroblasts and lymphatics were altered in response to hyperoxia. VEGF-D biology was interrogated by utilising mice with a null mutation in <i>Vegfd</i>, and qPCR was used to define mechanisms underlying phenotypes. Hyperoxia elicited expression of VEGF-D, a powerful lymphangiogenic growth factor that is expressed exclusively in lung fibroblasts. In response to hyperoxia, alveolar fibroblasts exhibited significant alterations to their transcriptional profile and changed signaling dynamics within the BPD microenvironment. Probing VEGF-D biology by genetic deletion revealed that VEGF-D deficiency worsened alveolar simplification in response to hyperoxia, exacerbated alveolar fluid accumulation, worsened inflammation, and deranged lymphatic architecture. These data identify an important interplay between alveolar fibroblasts, VEGF-D and lymphatics in regulating functional lymphangiogenesis and lymphatic vessel patterning in BPD that inform therapeutic and regenerative medicine strategies for this incurable disease.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962658","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":"The Acrolein - Lipopolysaccharide Mouse Model for Frequent Exacerbations in COPD.","authors":"Bernhard Fe Reiter, Natalie Bordag, Diana Schnoegl, Martina Delbeck, Tobias Madl, Hansjörg Habisch, Grazyna Kwapiszewska, Jörg Meding, Leigh M Marsh","doi":"10.1165/rcmb.2024-0507MA","DOIUrl":"https://doi.org/10.1165/rcmb.2024-0507MA","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) is a severe progressive lung disease, often caused by prolonged exposure to cigarette smoke and environmental factors. Pre-clinical COPD research predominately relies on chronic smoke or elastase animal models, each with their own advantages and limitations, such as limited pathophysiological insights or long treatment times. Here we describe a novel and time efficient mouse model of COPD based on bacterial lipopolysaccharide (LPS) and the reactive aldehyde acrolein (Acro). Mice were treated once per week for four weeks with a combination of both LPS and Acro. Histological, inflammatory, and metabolomic alterations were analysed by histological quantification, multicolour flow cytometry, and nuclear magnetic resonance (NMR). Acro/LPS treatment induced moderate airspace enlargement and bronchial remodelling. These structural changes were associated with a distinct inflammatory profile marked by an increase in macrophages, and T-helper cells, as well as increased cytokines, including CXCL11, IL-17a, and TNF-α. Strong inflammation, consisting of T-helper and B-cells was detected in the perivascular and peribronchial space, and increased macrophages in the alveolar regions. Additionally, intervention with the steroid dexamethasone induced a strong reduction in T-cells and macrophages and partially ameliorated histological alterations. Furthermore, we could detect alterations in the metabolome of serum and tissue, including an increase in COPD associated metabolites like trimethylamine N-oxide, as well as a misbalance in energy related metabolites and several amino acids. In summary, we can describe a practical, representative, and time efficient mouse model of COPD, with the potential to study the immunological and pathophysiological development of the disease.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955903","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":"Reversing Alcohol-Dependent Effects on HIV Replication: Are There Roles for Pioglitazone and N-Acetylcysteine?","authors":"Anne M Manicone, Jourdan E Brune","doi":"10.1165/rcmb.2025-0236ED","DOIUrl":"https://doi.org/10.1165/rcmb.2025-0236ED","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957577","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":"A Breath of Fresh Insight: Targeting CXCR4 in Early COPD.","authors":"Rebecca E Bignold, Jill R Johnson","doi":"10.1165/rcmb.2025-0235ED","DOIUrl":"https://doi.org/10.1165/rcmb.2025-0235ED","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962713","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":"Nerandomilast - A Multifrontal Therapeutic Approach to Lung Fibrosis.","authors":"Daniel Kalina, Malgorzata Wygrecka","doi":"10.1165/rcmb.2025-0140ED","DOIUrl":"https://doi.org/10.1165/rcmb.2025-0140ED","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966390","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":"Closing the Gap: Use of Polidocanol to Study Human Airway Epithelial Repair.","authors":"Irene H Heijink, Kingsley Okechukwu Nwozor, Tillie-Louise Hackett","doi":"10.1165/rcmb.2025-0165ED","DOIUrl":"https://doi.org/10.1165/rcmb.2025-0165ED","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961255","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":"May Highlights/Papers by Junior Investigators/NIH News.","authors":"","doi":"10.1165/rcmb.72i5RedAlert","DOIUrl":"https://doi.org/10.1165/rcmb.72i5RedAlert","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":"72 5","pages":"iii-iv"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956150","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":"A Developmental Step Along the 'Omics Journey.","authors":"James S Hagood","doi":"10.1165/rcmb.2024-0524ED","DOIUrl":"10.1165/rcmb.2024-0524ED","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"464-465"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12051909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674903","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}