{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T10:35:43Z","timestamp":1784975743151,"version":"3.55.0"},"reference-count":43,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Innate Immun"],"abstract":"<jats:p>&lt;p&gt;Introduction: Chronic obstructive pulmonary disease (COPD) is characterized by persistent airway remodeling and epithelial dysfunction, but the molecular mechanisms underlying these pathological changes remain unclear. This study aimed to investigate the role of ATP synthase subunit \u03b2 (ATP5B) in airway remodeling and epithelial cell heterogeneity in COPD. Methods: Single-cell RNA sequencing data from small airway epithelial tissues of smokers and nonsmokers were analyzed to identify key cell clusters and hub genes. ATP5B was identified by integrating differentially expressed genes and epithelial cell markers. Functional validation was performed using in vitro experiments with 2% cigarette smoke extract (CSE)-treated BEAS-2B cells and in vivo studies in a CS\/LPS-induced COPD mouse model. Molecular assays included RT-qPCR, Western blotting, ELISA, flow cytometry, and histological analysis. Gene set enrichment analysis (GSEA) was applied to explore potential signaling pathways. Results: Twelve distinct epithelial clusters were identified, and ATP5B emerged as a hub gene significantly upregulated in COPD. Silencing ATP5B reversed CSE-induced apoptosis, reduced pro-inflammatory cytokine release (IL-6, TNF-\u03b1), and suppressed epithelial-mesenchymal transition. In vivo, ATP5B knockdown alleviated airway inflammation and remodeling. GSEA and experimental validation confirmed that ATP5B promotes airway remodeling via activation of the Toll-like receptor (TLR) signaling pathway. Conclusion: These findings suggest that ATP5B may serve as a novel biomarker and therapeutic target for ATP5B plays a crucial role in airway remodeling in COPD by activating the TLR signaling pathway. &lt;\/p&gt;<\/jats:p>","DOI":"10.1159\/000547329","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T16:02:50Z","timestamp":1753718570000},"page":"414-431","source":"Crossref","is-referenced-by-count":5,"title":["Impact of Adenosine Triphosphate Synthase Subunit \u03b2 on TLR Signaling Pathway in Promoting Airway Remodeling and Heterogeneity of Small Airway Epithelial Cells in Chronic Obstructive Pulmonary Disease"],"prefix":"10.1159","volume":"17","author":[{"given":"Yabo","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanyu","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanwan","family":"Sui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanming","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianglin","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinyu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ci","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4546-926X","authenticated-orcid":false,"given":"Yamei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2025,7,28]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(22)00470-6"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccm.2020.06.007"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00121.2021"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01957"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2021.107839"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.4155\/fmc-2021-0010"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2021.08.005"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0165-2020"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2021.0137"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.81609"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2018.12.004"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1016\/j.prrv.2019.04.001"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrestox.4c00328"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.3390\/antiox13091058"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.7413"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1007\/s00408-024-00766-3"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-020-01442-9"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.2147\/copd.s161958"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3192"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4096"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-01767-y"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.031"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac1000"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1074"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00330.2013"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.2147\/copd.s424431"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-10-43"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.21037\/atm-20-2196"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1183\/09059180.00004413"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1177\/0960327121997986"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.2147\/copd.s250576"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2021.112050"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.163.6.9908135"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2019.103415"},{"key":"ref37","doi-asserted-by":"publisher","DOI":"10.2147\/copd.s173206"},{"key":"ref38","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-018-1145-8"},{"key":"ref39","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115614"},{"key":"ref40","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.08.009"},{"key":"ref41","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202216082"},{"key":"ref42","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00440"},{"key":"ref43","doi-asserted-by":"publisher","DOI":"10.1007\/s00408-022-00574-7"}],"container-title":["Journal 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