European Respiratory Journal最新文献

{"title":"Genome-wide association study reveals <i>CBX7</i> as a novel susceptibility gene associated with primary spontaneous pneumothorax in the Chinese Han population.","authors":"Leilei Xu, Dehua Ma, Bingjian Wang, Mengru Cai, Zhichong Wu, Shuwen Cheng, Minghui Cai, Yibing Ding, Xinxin Zhang, Qi Sun, Fengnan Niu, Hongyan Wu, Zhicheng Dai, Haiyan Min, Yanting Wen, Shiyu Song, Wei Zou, Chao Wang, Sufen Li, Jiaochen Wang, Jianfei Shen, Xinxin Wang, Aifen Lin, Xingbing Cao, Xinxin Yuan, Chao Xia, Zhongying Guo, Zhenhua Feng, Ronghui Du, Jun Qiao, Qi Gao, Benlong Shi, Saihu Mao, Tianming Chen, Haozhen Ren, Minhua Ye, Xiaowen Hu, Ping Hu, Zhengfeng Xu, Shilin Chen, Yong Qiu, Yong Wang, Qian Gao, Chengchu Zhu, Zezhang Zhu, Long Yi","doi":"10.1183/13993003.02110-2024","DOIUrl":"https://doi.org/10.1183/13993003.02110-2024","url":null,"abstract":"<p><strong>Background: </strong>Primary spontaneous pneumothorax is a rare disease commonly found in young adults with unknown etiology. We aimed to investigate the susceptibility genes and the downstream signaling involved in the development of primary spontaneous pneumothorax.</p><p><strong>Methods: </strong>We conducted the first large-scale genome-wide association study (GWAS) composed of 2223 patients and 3838 controls. The functional role of the novel susceptibility loci was investigated by both in-vivo and in-vitro assays. Gene expression profiling in lung epithelial cell lines was performed and conditional gene knockout mice were generated.</p><p><strong>Results: </strong>We identified four novel susceptibility loci at 14q32.2 near <i>C14orf177</i>, at 15q26.3 near <i>CHSY1</i>, at 16q23.1 near <i>CFDP1</i>, and at 22q13.1 near <i>CBX7</i>. The fine-mapping of 22q13.1 revealed a functional variant which regulated <i>CBX7</i> expression by disrupting the binding activity of transcription factor CREB1. Conditional knock-out of <i>Cbx7</i> in mouse lung epithelial cells resulted in lung cyst formation. Meanwhile, down-regulation of the <i>CBX7</i> elevated the expression of <i>MMP9</i> and <i>MMP16</i>, which are part of extracellular matrix regulators and may lead to lung injury.</p><p><strong>Conclusions: </strong>Our GWAS discovered four novel susceptibility loci of primary spontaneous pneumothorax and presented a mechanistic basis for the genetic association with primary spontaneous pneumothorax. The novel susceptibility gene <i>CBX7</i> and downstream <i>MMPs</i> signaling give a new clue to the pathogenesis of primary spontaneous pneumothorax.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clarification of author disclosures in the article \"Angiotensin converting enzyme 2 and angiotensin (1-7) axis in pulmonary arterial hypertension\".","authors":"","doi":"10.1183/13993003.52416-2019","DOIUrl":"https://doi.org/10.1183/13993003.52416-2019","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"65 6","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the AXL pathway: a promising strategy for pulmonary fibrosis.","authors":"Jennifer L Larson-Casey, A Brent Carter","doi":"10.1183/13993003.00114-2025","DOIUrl":"https://doi.org/10.1183/13993003.00114-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"65 6","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply: Spirometry remains the GOLD standard test for COPD diagnosis.","authors":"Dave Singh, Alvar Agusti, Claus Volgelmeier, David Halpin","doi":"10.1183/13993003.00794-2025","DOIUrl":"10.1183/13993003.00794-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"65 6","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12138026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accelerated epigenetic ageing worsens survival and mediates environmental stressors in fibrotic interstitial lung disease.","authors":"Gillian C Goobie, Daniel-Costin Marinescu, Ayodeji Adegunsoye, Jean Bourbeau, Christopher Carlsten, Rachel L Clifford, Dany Doiron, Qingling Duan, Kevin F Gibson, Amanda Grant-Orser, Ana I Hernandez Cordero, Kerri A Johannson, Daniel J Kass, Sharon E Kim, Janice M Leung, Xiaoyun Li, Wan Tan, Chen Xi Yang, S Mehdi Nouraie, Christopher J Ryerson, Tillie L Hackett, Yingze Zhang","doi":"10.1183/13993003.01618-2024","DOIUrl":"10.1183/13993003.01618-2024","url":null,"abstract":"<p><strong>Background: </strong>The role of epigenetic ageing in the environmental pathogenesis and prognosis of fibrotic interstitial lung disease (fILD) is unclear. We evaluated whether ambient particulate matter with diameter ≤2.5 μm (PM_2.5) and neighbourhood disadvantage exposures are associated with accelerated epigenetic ageing, and whether epigenetic age is associated with adverse clinical outcomes in patients with fILD.</p><p><strong>Methods: </strong>This multicentre, international, cohort study included patients with fILD from the University of Pittsburgh (UPitt, n=306) and University of British Columbia (UBC, n=170). 5-year PM_2.5 exposures were estimated using satellite-derived hybrid models. Neighbourhood disadvantage was calculated using US and Canadian census-based metrics. Epigenetic age difference (EAD=epigenetic age-chronological age) was calculated using GrimAge analysis of blood DNA methylation data. Linear models assessed associations of exposures with EAD. Cox models assessed associations of EAD with transplant-free survival. Causal mediation analysis evaluated EAD mediation of exposure-survival relationships.</p><p><strong>Results: </strong>Median epigenetic age was 11.7 years older than chronological age in patients with fILD. In combined cohort analysis, each interquartile range (IQR) increase in PM_2.5 was associated with 2.88 years (95% CI 1.39-4.38; p<0.001) increased EAD. In UPitt, each IQR neighbourhood disadvantage increase was associated with 1.16 years (95% CI 0.22-2.09; p=0.02) increased EAD. Increased EAD was associated with worse transplant-free survival (hazard ratio 1.17 per 1-year increase in EAD, 95% CI 1.10-1.24; p<0.001), with EAD mediating 40% of the PM_2.5-survival relationship and 59% of the neighbourhood disadvantage-survival relationship. Epigenetic age was also more strongly associated with transplant-free survival than chronological age.</p><p><strong>Conclusions: </strong>Epigenetic age acceleration is associated with worse survival and mediates adverse exposure impacts in fILD.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rbms1 promotes pulmonary fibrosis by stabilising Sumo2 mRNA to facilitate Smad4-SUMOylation and fibroblast activation.","authors":"Yingying Guo, Qianqian Wang, Yuhan Zhang, Lingxue Ren, Yuquan Wang, Yang Liu, Miao Liu, Xiaomu Tian, Qiudi Liu, Yi Chen, Jian Sun, Tongzhu Jin, Xinyue Wang, Yanbo Wang, Tianyu Li, Yuhong Zhou, Zhixin Li, Yunyan Gu, Baofeng Yang, Haihai Liang","doi":"10.1183/13993003.01667-2024","DOIUrl":"https://doi.org/10.1183/13993003.01667-2024","url":null,"abstract":"<p><p>The formation of myofibroblast foci constitutes a hallmark pathological feature of idiopathic pulmonary fibrosis (IPF), yet the mechanism remains elusive. RNA binding motif single-stranded interacting protein 1 (RBMS1), is known to be essential for proliferation and cell cycle progression; however, its role in pulmonary fibrosis remains to be clarified.This study aimed to systematically elucidate the role and underlying mechanism of RBMS1 in pulmonary fibrosis utilising mouse primary lung fibroblasts (mPLFs), fibroblast-specific Rbms1 deletion and overexpression mice models, and lung samples from IPF patients.RBMS1 was highly expressed in both IPF patient lungs and murine bleomycin (BLM)-induced fibrotic lesions. Notably, elevated RBMS1 expression was observed in the cytoplasm of mPLFs following TGF-β1 stimulation. Rbms1 promoted lung fibroblast activation, while knockdown of Rbms1 mitigated TGF-β1-induced fibrogenesis. <i>In vivo</i>, overexpression impaired lung function and exacerbated pulmonary fibrosis, whereas fibroblast-specific Rbms1 deletion exhibited a significant reduction in fibrosis post-BLM treatment. Mechanistically, Rbms1 binds to Sumo2 3'UTR, enhancing the mRNA stability. Furthermore, Rbms1 induced the SUMOylation of Smad4, with lysine 158 identified as a critical SUMOylation site. Meanwhile, Sumo2 knockdown alleviated the Rbms1-driven exacerbation of pulmonary fibrosis. Importantly, the nortriptyline pharmacologically inhibited RBMS1 to ameliorate pulmonary fibrosis in mice.Collectively, our study sheds light on the regulatory role of RBMS1 in pulmonary fibrosis, highlighting its therapeutic potential for targeted antifibrotic strategies.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping idiopathic pulmonary fibrosis: how cellular niches fuel pathogenic plasma cell accumulation.","authors":"Doumet Georges Helou, Nicolas Riteau","doi":"10.1183/13993003.00036-2025","DOIUrl":"https://doi.org/10.1183/13993003.00036-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"65 6","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Theratyping in cystic fibrosis: filling the knowledge gaps.","authors":"Iwona Pranke, Isabelle Sermet-Gaudelus","doi":"10.1183/13993003.00778-2025","DOIUrl":"https://doi.org/10.1183/13993003.00778-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"65 6","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of AXL ameliorates pulmonary fibrosis <i>via</i> attenuation of M2 macrophage polarisation.","authors":"Dong Ha Kim, Ho Cheol Kim, Kyungtaek Im, In-Jeoung Baek, Yun Jung Choi, Hyeonjeong Lee, Da-Som Kim, Chae Won Lee, JaeYi Jeong, Kyosun Ban, Sang-Yeob Kim, Wonjun Ji, Jae Cheol Lee, Hyun-Yi Kim, Yoonji Lee, Yeongin Yang, Miyong Yun, Chang Min Choi, Jin Kyung Rho","doi":"10.1183/13993003.00615-2024","DOIUrl":"10.1183/13993003.00615-2024","url":null,"abstract":"<p><strong>Rationale: </strong>Although a relationship between the growth arrest-specific 6 (GAS6)/anexelekto (AXL) pathway and pulmonary fibrosis has been suggested, the precise mechanisms and clinical implications of the AXL pathway in idiopathic pulmonary fibrosis are still unclear.</p><p><strong>Methods: </strong>Constitutive and conditional AXL-knockout mice were generated and injected with bleomycin to induce pulmonary fibrosis. The expression of AXL and macrophage subtypes in bleomycin-injected mice and patients with idiopathic pulmonary fibrosis was analysed using flow cytometry. The therapeutic effects of the AXL inhibitors were examined.</p><p><strong>Results: </strong>AXL-deficient mice were resistant to bleomycin-induced pulmonary fibrosis and had a lower degree of M2-like macrophage differentiation than wild-type mice. Interestingly, AXL expression in monocytes was enhanced according to the progression of bleomycin-induced pulmonary fibrosis, and these results were especially prominent in lymphocyte antigen 6C (Ly6C)^high monocytes. Gene silencing or inhibitor treatment with AXL inhibited the differentiation of M2-like macrophages during bone marrow-derived macrophage differentiation. These results were confirmed through experiments using <i>AXL^fl/flLysMCre+</i> mice and systems with depletion and reconstitution of macrophages. In line with these results, patients with severe idiopathic pulmonary fibrosis had high AXL expression in monocytes, high GAS6 levels and an enhanced population of M2-like macrophages compared to those with mild idiopathic pulmonary fibrosis. Lastly, treatment with AXL inhibitors ameliorated bleomycin-induced pulmonary fibrosis and improved survival rates.</p><p><strong>Conclusions: </strong>The AXL pathway in classical monocytes contributes to pulmonary fibrosis progression through the induction of M2-like macrophage differentiation. Therefore, targeting AXL may be a promising therapeutic option for pulmonary fibrosis.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12138030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of fibrotic-related extracellular vesicle microRNAs with lung involvement in systemic sclerosis.","authors":"Julien Guiot, Béatrice André, Judith Potjewijd, Pierre Jacquerie, Sébastien Cremers, Monique Henket, Latifa Idoufkir, Claire Remacle, Rachid Tobal, Laurie Giltay, Catherine Moermans, Fanny Gester, Barbara Polese, Malik Hamaïdia, Ingrid Struman, Edouard Louis, Michel Malaise, Dominique de Seny, Pieter van Paassen, Renaud Louis, Clio Ribbens, Makon-Sébastien Njock","doi":"10.1183/13993003.00276-2024","DOIUrl":"10.1183/13993003.00276-2024","url":null,"abstract":"<p><strong>Background: </strong>There is a pressing need to identify early biomarkers of lung involvement in systemic sclerosis to start antifibrotic therapy as soon as possible. We aimed to identify extracellular vesicle-derived microRNAs (miRNAs) that are differentially expressed between systemic sclerosis patients with and without interstitial lung disease, and to explore their diagnostic value and functional properties.</p><p><strong>Methods: </strong>Small extracellular vesicles derived from plasma were isolated from 91 well-characterised patients with systemic sclerosis with (n=45) and without (n=46) interstitial lung disease and 43 matched healthy subjects. Small RNA-sequencing followed by quantitative reverse transcriptase PCR were used to identify and validate small extracellular vesicle miRNAs associated with systemic sclerosis-associated interstitial lung disease. Correlations between systemic sclerosis-associated interstitial lung disease miRNAs and clinical parameters were assessed, as well as the effect of related miRNAs/small extracellular vesicles on fibrosis.</p><p><strong>Results: </strong>We identified a four-miRNA signature associated with interstitial lung disease in the context of systemic sclerosis (miR-584-5p, miR-744-5p, miR-1307-3p and miR-10b-5p) (area under the receiver operating characteristic curve 0.85, 95% CI 0.76-0.94; p<0.0001). Deeper analysis revealed a correlation of these candidates with pulmonary function tests (diffusing capacity of the lung for carbon monoxide and forced vital capacity), highlighting their use in monitoring lung fibrosis progression in systemic sclerosis patients. Furthermore, small extracellular vesicle miRNAs associated with systemic sclerosis-associated interstitial lung disease are positively correlated with and enriched in circulating lymphocytes, suggesting that these immune cells are their cellular source. Finally, functional studies highlighted altered functional properties of small extracellular vesicles in the context of systemic sclerosis-associated interstitial lung disease, mainly due to the transfer of profibrotic miR-584-5p in lung fibroblasts.</p><p><strong>Conclusions: </strong>Our small extracellular vesicle-based biomarker approach identified a promising four‑miRNA signature characteristic of interstitial lung disease in systemic sclerosis patients. Furthermore, the profibrotic properties of small extracellular vesicles associated with systemic sclerosis-associated interstitial lung disease suggest a prominent role of these vesicles in systemic sclerosis severity.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12138034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}