{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T20:36:02Z","timestamp":1761597362016},"reference-count":41,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,10,1]]},"abstract":"<jats:p>Cholestatic liver injury may activate HSCs (hepatic stellate cells) to a profibrogenic phenotype, contributing to liver fibrogenesis. We have previously demonstrated the involvement of TLR (Toll-like receptor) 7\u00a0in the pathogenesis of biliary atresia. In the present study we investigated the ability of TLR7 to modulate the profibrogenic phenotype in HSCs. Obstructive jaundice was associated with significant down-regulation of TLR7. Primary HSCs isolated from BDL (bile duct ligation) rats with obstructive jaundice exhibited reduced expression of TLR7 and increased expression of \u03b1-SMA (\u03b1-smooth muscle actin) and collagen-\u03b11 compared with sham rats, reflecting HSC-mediated changes. Treatment of primary activated rat HSCs and rat T6 cells with CL075, a TLR7 and TLR8 ligand, significantly decreased expression of MCP-1 (monocyte chemotactic protein-1), TGF-\u03b21 (transforming growth factor-\u03b21), collagen-\u03b11 and MMP-2 (matrix metalloproteinase-2), and inhibited cell proliferation and migration. In contrast, silencing TLR7 expression with shRNA (short hairpin RNA) in T6 cells effectively blocked the effects of CL075 stimulation, reversing the changes in MCP-1, TGF-\u03b21 and collagen-\u03b11 expression and accelerating cell migration. Our results indicate that obstructive jaundice is associated with down-regulation of TLR7 and up-regulation of profibrogenic gene expression in HSCs. Selective activation of TLR7 may modulate the profibrogenic phenotype in activated HSCs associated with cholestatic liver injury.<\/jats:p>","DOI":"10.1042\/bj20112058","type":"journal-article","created":{"date-parts":[[2012,7,9]],"date-time":"2012-07-09T10:07:33Z","timestamp":1341828453000},"page":"25-34","update-policy":"http:\/\/dx.doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Selective activation of Toll-like receptor 7 in activated hepatic stellate cells may modulate their profibrogenic phenotype"],"prefix":"10.1042","volume":"447","author":[{"given":"Ming-Huei","family":"Chou","sequence":"first","affiliation":[{"name":"Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and the Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan"},{"name":"Institute of Basic Medical Sciences, National Chang Kung University, Tainan 701, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying-Hsien","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and the Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsun-Mei","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, National Chang Kung University, Tainan 701, Taiwan"},{"name":"Departments of Laboratory Medicine and Medical Research, E-DA Hospital\/I-SHOU University, Kaohsiung 82445, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yung-Ying","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and the Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Po-Chin","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and the Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih-Sung","family":"Hsieh","sequence":"additional","affiliation":[{"name":"PingTung Christian Hospital Department of Medical Research, PingTung 900, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiin-Haur","family":"Chuang","sequence":"additional","affiliation":[{"name":"Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and the Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2012,9,12]]},"reference":[{"key":"2021112217322178800_B1","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1053\/j.gastro.2008.03.003","article-title":"Mechanisms of hepatic fibrogenesis","volume":"134","author":"Friedman","year":"2008","journal-title":"Gastroenterology"},{"key":"2021112217322178800_B2","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/nrgastro.2010.97","article-title":"Evolving challenges in hepatic fibrosis","volume":"7","author":"Friedman","year":"2010","journal-title":"Nat. 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