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Recovery from liver fibrosis is accompanied by hepatocyte regeneration, matrix degradation, and HSC apoptosis. Using mice bearing a mutated collagen\u2010I gene (r\/r mice), which confers resistance to collagenase degradation, we have investigated the hypothesis that collagen\u2010I degradation is critical to HSC apoptosis and hepatocyte regeneration during recovery from liver fibrosis. During a 28\u2010day recovery period after 8 wk of CCl4 treatment, wild\u2010type (WT) livers had significantly (43%) decreased hydroxyproline (OHP) content. In r\/r livers, however, OHP content remained elevated at peak fibrosis levels. Expressed markers of activated HSC (\u03b1\u2010smooth muscle actin, collagen\u2010I), elevated at peak fibrosis, dropped to control levels in WT livers after 28 days but remained raised in the r\/r livers. Moreover, relative to WT livers, r\/r livers had significantly reduced stellate cell apoptosis and hepatocyte regeneration during the recovery period. Using extracted collagen\u2010I from each genotype as culture substrata, relative to r\/r, we show that WT collagen\u2010I promotes hepatocyte proliferation via stimulation of integrin \u03b1v\u03b2\n                    <jats:sub>3<\/jats:sub>\n                    . Failure to degrade collagen\u2010I critically impairs HSC apoptosis and may prevent the effective restoration of hepatocyte mass in liver fibrosis.\n                  <\/jats:p>","DOI":"10.1096\/fj.02-0494fje","type":"journal-article","created":{"date-parts":[[2003,1,13]],"date-time":"2003-01-13T19:44:17Z","timestamp":1042487057000},"page":"47-49","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":176,"title":["Mutation in collagen\u2010I that confers resistance to the action of collagenase results in failure of recovery from CCl\n                    <sub>4<\/sub>\n                    \u2010induced liver fibrosis, persistence of activated hepatic stellate cells, and diminished hepatocyte regeneration"],"prefix":"10.1096","volume":"17","author":[{"given":"Razao","family":"Issa","sequence":"first","affiliation":[{"name":"Liver Research Group and Department of Histopathology, Infection, Inflammation and Repair, South Lab and Path Block University of Southampton, Southampton General Hospital  Southampton SO16 6YD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"Zhou","sequence":"additional","affiliation":[{"name":"Liver Research Group and Department of Histopathology, Infection, Inflammation and Repair, South Lab and Path Block University of Southampton, Southampton General Hospital  Southampton SO16 6YD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Trim","sequence":"additional","affiliation":[{"name":"Liver Research Group and Department of Histopathology, Infection, Inflammation and Repair, South Lab and Path Block University of Southampton, Southampton General Hospital  Southampton SO16 6YD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"Millward\u2010Sadler","sequence":"additional","affiliation":[{"name":"Liver Research Group and Department of Histopathology, Infection, Inflammation and Repair, South Lab and Path Block University of Southampton, Southampton General Hospital  Southampton SO16 6YD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Krane","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Massachusetts General Hospital  Boston MA 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Benyon","sequence":"additional","affiliation":[{"name":"Liver Research Group and Department of Histopathology, Infection, Inflammation and Repair, South Lab and Path Block University of Southampton, Southampton General Hospital  Southampton SO16 6YD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Iredale","sequence":"additional","affiliation":[{"name":"Liver Research Group and Department of Histopathology, Infection, Inflammation and Repair, South Lab and Path Block University of Southampton, Southampton General Hospital  Southampton SO16 6YD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2002,11,15]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1711700203"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199306243282508"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1042\/cs0920103"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.24.8681"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114886"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114270"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2870701"},{"key":"e_1_2_6_9_1","doi-asserted-by":"crossref","first-page":"369A","DOI":"10.1016\/0270-9139(95)95199-7","article-title":"Membrane\u2010type matrix metalloproteinase is produced by hepatic stellate cells","volume":"22","author":"Hovell C. 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