{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T14:02:14Z","timestamp":1787752934983,"version":"build-2784847793"},"reference-count":74,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,23]],"date-time":"2023-04-23T00:00:00Z","timestamp":1682208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Polish National Science Centre","doi-asserted-by":"publisher","award":["2019\/03\/X\/NZ3\/01801"],"award-info":[{"award-number":["2019\/03\/X\/NZ3\/01801"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"Polish National Science Centre","doi-asserted-by":"publisher","award":["2015\/17\/B\/NZ3\/02248"],"award-info":[{"award-number":["2015\/17\/B\/NZ3\/02248"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"Polish National Science Centre","doi-asserted-by":"publisher","award":["2019\/03\/X\/NZ3\/01801"],"award-info":[{"award-number":["2019\/03\/X\/NZ3\/01801"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"Polish National Science Centre","doi-asserted-by":"publisher","award":["2015\/17\/B\/NZ3\/02248"],"award-info":[{"award-number":["2015\/17\/B\/NZ3\/02248"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The airway wall remodeling observed in asthma is associated with subepithelial fibrosis and enhanced activation of human bronchial fibroblasts (HBFs) in the fibroblast to myofibroblast transition (FMT), induced mainly by transforming growth factor-\u03b2 (TGF-\u03b2). The relationships between asthma severity, obesity, and hyperlipidemia suggest the involvement of peroxisome proliferator-activated receptors (PPARs) in the remodeling of asthmatic bronchi. In this study, we investigated the effect of PPAR\u03b4 ligands (GW501516 as an agonist, and GSK0660 as an antagonist) on the FMT potential of HBFs derived from asthmatic patients cultured in vitro. This report shows, for the first time, the inhibitory effect of a PPAR\u03b4 agonist on the number of myofibroblasts and the expression of myofibroblast-related markers\u2014\u03b1-smooth muscle actin, collagen 1, tenascin C, and connexin 43\u2014in asthma-related TGF-\u03b2-treated HBF populations. We suggest that actin cytoskeleton reorganization and Smad2 transcriptional activity altered by GW501516 lead to the attenuation of the FMT in HBF populations derived from asthmatics. In conclusion, our data demonstrate that a PPAR\u03b4 agonist stimulates antifibrotic effects in an in vitro model of bronchial subepithelial fibrosis. This suggests its potential role in the development of a possible novel therapeutic approach for the treatment of subepithelial fibrosis during asthma.<\/jats:p>","DOI":"10.3390\/ijms24097721","type":"journal-article","created":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T04:01:23Z","timestamp":1682308883000},"page":"7721","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["PPAR\u03b4 Agonist GW501516 Suppresses the TGF-\u03b2-Induced Profibrotic Response of Human Bronchial Fibroblasts from Asthmatic Patients"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3325-7916","authenticated-orcid":false,"given":"Milena","family":"Paw","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5807-2440","authenticated-orcid":false,"given":"Dawid","family":"Wnuk","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5523-1215","authenticated-orcid":false,"given":"Zbigniew","family":"Madeja","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1482-2959","authenticated-orcid":false,"given":"Marta","family":"Michalik","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"246","DOI":"10.3389\/fped.2019.00246","article-title":"Epidemiology of Asthma in Children and Adults","volume":"7","author":"Dharmage","year":"2019","journal-title":"Front. 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