{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T09:10:30Z","timestamp":1776157830264,"version":"3.50.1"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T00:00:00Z","timestamp":1741046400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>This study aims to investigate the role of integrin \u03b14 (ITGA4) in the inhibition of hepatic stellate cells (HSCs) fibrosis by <jats:italic>Periplaneta americana<\/jats:italic> extract (PAE), as well as to explore its molecular mechanisms. <jats:italic>In vitro<\/jats:italic> experiments utilized TGF\u03b2-induced LX2 and HSC-T6 cells to examine the anti-fibrotic effects of PAE, particularly through ITGA4 overexpression, to elucidate its involvement in PAE-mediated inhibition via the PI3K-AKT signaling pathway. Cell viability was assessed using the CCK-8 method, and the IC<jats:sub>50<\/jats:sub> for PAE was determined through statistical analysis. We evaluated cell proliferation using scratch and EDU assays, and migration capabilities using Transwell assays. Molecular mechanisms were investigated through western blot (WB), quantitative PCR (QPCR), and transcriptome analysis. Results indicate that PAE reduces hepatic fibrosis by curbing hepatic stellate cells (HSCs) proliferation, migration, collagen synthesis, inflammatory cytokine production, and epithelial-mesenchymal transition (EMT). Additionally, while PAE suppressed ITGA4\u2019s high expression in activated HSCs, ITGA4 overexpression counteracted PAE\u2019s effects on HSC proliferation, migration, and collagen synthesis. These findings demonstrate that PAE primarily mitigates fibrosis in activated HSCs by inhibiting ITGA4, thus delivering anti-fibrotic effects in the liver.<\/jats:p>","DOI":"10.3389\/fphar.2025.1517491","type":"journal-article","created":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T07:10:54Z","timestamp":1741072254000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Role of integrin \u03b14 in the inhibition of fibrosis in activated hepatic stellate cells by Periplaneta americana extract"],"prefix":"10.3389","volume":"16","author":[{"given":"Ying","family":"Fang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ye","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dingchun","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Miu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kexuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jv","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijuan","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinting","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingyan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lechun","family":"Lv","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wu","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e150059","DOI":"10.1172\/jci.insight.150059","article-title":"GATA4 induces liver fibrosis regression by deactivating hepatic stellate cells","volume":"6","author":"Arroyo","year":"2021","journal-title":"JCI Insight"},{"key":"B2","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1002\/med.21601","article-title":"The role of integrins in the pathogenesis of inflammatory bowel disease: approved and investigational anti-integrin therapies","volume":"40","author":"Dotan","year":"2020","journal-title":"Med. 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