{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:17:08Z","timestamp":1787015828115,"version":"build-2736575974"},"reference-count":37,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2015,1,20]],"date-time":"2015-01-20T00:00:00Z","timestamp":1421712000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology of Japan","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2015,8]]},"abstract":"Abstract<\/jats:title>\n \n Background & Aims<\/jats:title>\n \n Obesity\u2010related adipocytokine dysregulation is known to accelerate liver fibrosis progression. Recently, a natural Wnt5a inhibitor, secreted frizzled\u2010related protein 5 (Sfrp5), was identified as a novel adipocytokine that has reduced expression in obese adipose tissue in both rodents and human. In addition, hepatic gene expression of\n Wnt5a<\/jats:italic>\n and its receptor frizzled 2 (\n Fz2<\/jats:italic>\n ) is elevated during fibrosis progression. Therefore, Sfrp5 could have biological significance in liver fibrosis.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We first investigated the effects of Sfrp5 on primary cultured mouse hepatic stellate cells (\n HSC<\/jats:styled-content>\n s)\n in vitro<\/jats:italic>\n . Next, to elucidate the roles of Sfrp5 in liver fibrosis, we investigated a carbon\u2010tetrachloride (\n CC<\/jats:styled-content>\n l\n 4<\/jats:sub>\n )\u2010induced liver fibrosis model using\n Sfrp5<\/jats:italic>\n knockout (\n KO<\/jats:styled-content>\n ) and wild type (\n WT<\/jats:styled-content>\n ) mice\n in vivo<\/jats:italic>\n . Each mouse was injected intraperitoneally with\n CC<\/jats:styled-content>\n l\n 4<\/jats:sub>\n (0.5\u00a0ml\/kg) or olive oil as a single dose (acute liver injury model), or twice a week for 6\u00a0weeks (liver fibrosis model).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In\n in vitro<\/jats:italic>\n studies, Wnt5a enhanced both proliferation and migration of\n HSC<\/jats:styled-content>\n s, and these effects could be completely blocked by Sfrp5. Moreover, si\n RNA<\/jats:styled-content>\n knockdown of\n Fz2<\/jats:italic>\n in\n HSC<\/jats:styled-content>\n s could block the effects of Wnt5a on both\n HSC<\/jats:styled-content>\n proliferation and migration. In\n in vivo<\/jats:italic>\n studies, there were no differences in the\n CC<\/jats:styled-content>\n l\n 4<\/jats:sub>\n \u2010induced liver injury between\n KO<\/jats:styled-content>\n and\n WT<\/jats:styled-content>\n mice. Hepatic\n Wnt5a<\/jats:italic>\n gene expression and plasma Wnt5a levels significantly increased after a single\u00a0\n CC<\/jats:styled-content>\n l\n 4<\/jats:sub>\n injection in both mice.\n Sfrp5<\/jats:italic>\n knockout significantly enhanced\n CC<\/jats:styled-content>\n l\n 4<\/jats:sub>\n \u2010induced liver fibrosis.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Our findings demonstrate that Sfrp5 may ameliorate mouse liver fibrosis through inhibition of Wnt5a\/Fz2 signalling.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/liv.12757","type":"journal-article","created":{"date-parts":[[2014,12,9]],"date-time":"2014-12-09T06:32:35Z","timestamp":1418106755000},"page":"2017-2026","source":"Crossref","is-referenced-by-count":41,"title":["Secreted frizzled\u2010related protein 5 (Sfrp5) decreases hepatic stellate cell activation and liver fibrosis"],"prefix":"10.1111","volume":"35","author":[{"given":"Norihiro","family":"Chatani","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology Osaka University Graduate School of Medicine Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Kamada","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Osaka University Graduate School of Medicine Suita Osaka Japan"},{"name":"Department of Molecular Biochemistry & Clinical Investigation Osaka University Graduate School of Medicine Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kizu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Osaka University Graduate School of Medicine Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Ogura","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Osaka University Graduate School of Medicine Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunimaro","family":"Furuta","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Osaka University Graduate School of Medicine Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayumi","family":"Egawa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Osaka University Graduate School of Medicine Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"Hamano","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Osaka University Graduate School of Medicine Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisao","family":"Ezaki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Osaka University Graduate School of Medicine Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichi","family":"Kiso","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Osaka University Graduate School of Medicine Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiko","family":"Shimono","sequence":"additional","affiliation":[{"name":"TransGenic Inc Kobe Hyogo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriyuki","family":"Ouchi","sequence":"additional","affiliation":[{"name":"Department of Molecular Cardiology Nagoya University Graduate School of Medicine Nagoya Aichi 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