{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T01:49:20Z","timestamp":1789955360269,"version":"4.0.1"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":5175,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,7]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Transforming growth factor \u03b2 (TGF\u2013\u03b2) is the most potent profibrogenic mediator in liver fibrosis. Although Smad proteins have been identified as intracellular mediators in the TGF\u2013\u03b2 signaling pathway, the function of individual Smad proteins remains poorly understood. The aim of this study was to explore the contribution of Smad3 in mediating TGF\u2013\u03b2 responses in a model of acute liver injury\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      and in culture\u2013activated hepatic stellate cells (HSCs). Wild\u2013type, Smad3 heterozygous or Smad3 homozygous knockout mice were treated with a single intragastric administration of CCl\n                      <jats:sub>4<\/jats:sub>\n                      . After 72 hours, the induction of hepatic collagen \u03b11(I) and \u03b12(I) messenger RNA (mRNA) levels in Smad3 knockout mice was only 42% and 64%, respectively, of the levels induced in wild\u2013type mice. However, smooth muscle \u03b1\u2013actin (\u03b1\u2013SMA) was expressed at a slightly higher level in livers from knockout mice compared with wild\u2013type mice. In culture\u2013activated HSCs from Smad3 knockout mice, collagen \u03b11(I) mRNA was 73% of wild\u2013type HSCs, but \u03b1\u2013SMA expression was the same. HSCs from knockout mice showed a higher proliferation rate than wild\u2013type HSCs. Smad3\u2013deficient HSCs did not form TGF\u2013\u03b21-induced Smad\u2013containing DNA\u2013binding complexes. In conclusion, (1) maximal expression of collagen type I in activated HSCs requires Smad3\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      and in culture; (2) Smad3 is not necessary for HSC activation as assessed by \u03b1\u2013SMA expression; (3) Smad3 is necessary for inhibition of proliferation of HSCs, which might be TGF\u2013\u03b2-dependent; and (4) Smad3 is required for TGF\u2013\u03b21-mediated Smad\u2013containing DNA\u2013binding complex formation in cultured HSCs.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1053\/jhep.2001.25349","type":"journal-article","created":{"date-parts":[[2002,8,24]],"date-time":"2002-08-24T23:46:10Z","timestamp":1030232770000},"page":"89-100","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":216,"title":["The Role of Smad3 in Mediating Mouse Hepatic Stellate Cell Activation"],"prefix":"10.1097","volume":"34","author":[{"given":"Bernd","family":"Schnabl","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young O.","family":"Kweon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua P.","family":"Frederick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Fan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Rippe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Brenner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1053%2Fjhep.2001.25349","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-200107000-00014","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T06:34:40Z","timestamp":1733034880000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-200107000-00014"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,7]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2001]]}},"URL":"https:\/\/doi.org\/10.1053\/jhep.2001.25349","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[2001,7]]}}}