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We present an innovative therapy based on the assignment of inactivated enzymes acting as scavengers for TIMP\u20101. Hepatic fibrosis was induced in BALB\/c mice by repetitive intraperitoneal CCl\n                    <jats:sub>4<\/jats:sub>\n                    injection. The animals were treated with proteolytic inactive matrix metalloproteinase\u20109 mutants (E402Q, H401A, E402H\/H411E) using adenovirus\u2010mediated gene transfer. Application of these MMP\u20109 mutants inhibited fibrogenesis, which was indicated by decreasing portal and periportal accumulation of collagen. Total hydroxyproline of liver tissue, the morphometric stage of fibrosis as well as mRNA expression of marker proteins for hepatic fibrosis in livers of E402Qand H401A\u2010treated mice were significantly reduced. MMP\u20109 mutants suppressed transdifferentiation of hepatic stellate cells to the myofibroblast like phenotype in vitro and in vivo. Moreover, adenoviral application of the mutants MMP\u20109\u2010H401A and \u2010E402Q led to increased apoptosis of activated hepatic stellate cells, thought to be the main promoters of hepatic fibrosis. Application of MMP\u20109 mutants as TIMP\u20101 scavengers may provide a new therapeutic strategy for hepatic fibrosis.\u2014Roderfeld, M., Weiskirchen, R., Wagner, S., Berres, M.\u2010L., Henkel, C., Gr\u00f6tzinger, J., Gressner, A. M., Matern, S., Roeb, E. Inhibition of hepatic fibrogenesis by matrix metalloproteinase\u20109 mutants in mice.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    20, 444\u2013454 (2006)\n                  <\/jats:p>","DOI":"10.1096\/fj.05-4828com","type":"journal-article","created":{"date-parts":[[2006,2,28]],"date-time":"2006-02-28T15:42:59Z","timestamp":1141141379000},"page":"444-454","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":115,"title":["Inhibition of hepatic fibrogenesis by matrix metalloproteinase\u20109 mutants in mice"],"prefix":"10.1096","volume":"20","author":[{"given":"Martin","family":"Roderfeld","sequence":"first","affiliation":[{"name":"Department of Internal Medicine III RWTH University Hospital Aachen  Aachen Germany"},{"name":"Department of Internal Medicine II Justus\u2010Liebig University  Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Weiskirchen","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Pathobiochemistry RWTH University Hospital Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Wagner","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III RWTH University Hospital Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Luise","family":"Berres","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III RWTH University Hospital Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinna","family":"Henkel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III RWTH University Hospital Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Gr\u00f6tzinger","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry Christian\u2010Albrechts\u2010University Kiel  Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel M.","family":"Gressner","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Pathobiochemistry RWTH University Hospital Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siegfried","family":"Matern","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III RWTH University Hospital Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elke","family":"Roeb","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III RWTH University Hospital Aachen  Aachen Germany"},{"name":"Department of Internal Medicine II Justus\u2010Liebig University  Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,3]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"111","article-title":"Tissue inhibitors of metalloproteinases: structure, regulation and biological functions","volume":"74","author":"Gomez D. 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