{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T05:50:46Z","timestamp":1791093046615,"version":"4.1.0"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2002,5,1]],"date-time":"2002-05-01T00:00:00Z","timestamp":1020211200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2003,12,30]],"date-time":"2003-12-30T00:00:00Z","timestamp":1072742400000},"content-version":"vor","delay-in-days":608,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"National Institutes of Health to D.C.R.","award":["R01 DK50574"],"award-info":[{"award-number":["R01 DK50574"]}]},{"name":"National Institutes of Health to D.C.R.","award":["R01 DK54038"],"award-info":[{"award-number":["R01 DK54038"]}]},{"name":"Burroughs Wellcome Fund to"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,5]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Transforming growth factor (TGF) \u03b2 isoforms (in particular, TGF-\u03b21) play a central role in the fibrogenic response to injury in many organs, including the liver. Although TGF-\u03b2 is clearly important in fibrogenesis, a number of issues related to therapeutic antagonism have emerged. For example, the long-term effect of TGF-\u03b2 antagonism is unknown; furthermore, controversy exists as to appropriate levels of TGF-\u03b2 inhibition. Therefore, we aimed to examine TGF-\u03b2 in models of chronic liver injury and to determine whether an <jats:bold>in vivo<\/jats:bold> dose-response relationship exists for inhibition of TGF-\u03b2. Liver injury was induced in BALB\/c mice by administering carbon tetrachloride for 4 or 8 weeks. TGF-\u03b2 binding was inhibited with a soluble TGF-\u03b2 type II receptor (STR) construct, administered intraperitoneally over a dose range of 4.0, 1.0, 0.4, or 0.1 mg\/kg twice weekly during fibrogenesis. Fibrogenesis was assessed by measurement of type I collagen messenger RNA (mRNA) expression and by quantitative morphometric analysis. In the 4-week study, STR at concentrations of 4.0, 1.0, and 0.1 mg\/kg reduced type I collagen mRNA expression by 31%, 49%, and 60% compared with immunoglobulin (Ig) G controls, respectively. In the 8-week study, lower concentrations of STR (0.1 mg\/kg) also had the greatest effect on type I collagen mRNA expression. Quantitative morphometrics similarly showed that lower concentrations of STR were the most antifibrogenic. In conclusion, the results confirm the antifibrotic effect of inhibiting TGF-\u03b2 in chronic hepatic wounding and, moreover, show that its <jats:bold>in vivo<\/jats:bold> effect in the mouse is dose dependent. Such findings have major translational implications for therapeutic strategies aimed at TGF-\u03b2.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1053\/jhep.2002.32673","type":"journal-article","created":{"date-parts":[[2003,2,17]],"date-time":"2003-02-17T22:18:10Z","timestamp":1045520290000},"page":"1022-1030","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":135,"title":["Dose-dependent inhibition of hepatic fibrosis in mice by a TGF-\u03b2 soluble receptor: Implications for antifibrotic therapy"],"prefix":"10.1097","volume":"35","author":[{"given":"Yutaka","family":"Yata","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Gotwals","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Koteliansky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Don C.","family":"Rockey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"10.1053\/jhep.2002.32673-BIB1|cit1","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1172\/JCI114886","article-title":"Extracellular matrix gene expression increases preferentially in rat lipocytes and sinusoidal endothelial cells during hepatic fibrosis in vivo","volume":"86","author":"Maher","year":"1990","journal-title":"J Clin Invest"},{"key":"10.1053\/jhep.2002.32673-BIB2|cit2","first-page":"59","article-title":"Cellular localization of type I III and IV procollagen gene transcripts in normal and fibrotic human liver","volume":"137","author":"Milani","year":"1990","journal-title":"Am J Pathol"},{"key":"10.1053\/jhep.2002.32673-BIB3|cit3","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1053\/jhep.2000.20243","article-title":"Mechanisms and therapy of hepatic fibrosis: report of the AASLD Single Topic Basic Research Conference","volume":"32","author":"Friedman","year":"2000","journal-title":"Hepatology"},{"key":"10.1053\/jhep.2002.32673-BIB4|cit4","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1083\/jcb.108.6.2477","article-title":"In vitro and in vivo association of transforming growth factor-beta 1 with hepatic fibrosis","volume":"108","author":"Czaja","year":"1989","journal-title":"J Cell Biol"},{"key":"10.1053\/jhep.2002.32673-BIB5|cit5","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1172\/JCI114643","article-title":"Cellular distribution of transforming growth factor-beta 1 and procollagen types I, III, and IV transcripts in carbon tetrachloride-induced rat liver fibrosis","volume":"85","author":"Nakatsukasa","year":"1990","journal-title":"J Clin Invest"},{"key":"10.1053\/jhep.2002.32673-BIB6|cit6","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1056\/NEJM199104043241401","article-title":"Transforming growth factors beta 1 and alpha in chronic liver disease. 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