Delivery of matrix metalloproteinase-1 attenuates established liver XXXX in the @entity35 .

@entity1 @entity7008 @entity1603 @entity82 @entity3334 @entity35 @entity1575
BACKGROUND _ AIMS: During hepatic fibrogenesis, the hepatic extracellular matrix changes to fibrillar collagens types I and III, and @entity82 is believed to produce an irreversible scar. In this study, we investigated whether gene delivery of @entity1 @entity3334 , which degrades collagens types I and type III, would attenuate established @entity1575 in the @entity35 , induced by either @entity7008 or bile duct ligation. METHODS: Hepatic @entity82 induced by @entity7008 for 7 weeks was persistent for at least 2 months, even after discontinuation of the treatment. The @entity35 were infected once with a recombinant adenovirus, Ad5MMP-1, into which @entity1 pro- @entity1 @entity3334 complementary DNA was packaged, or with a control adenovirus, Ad5LacZ. RESULTS: In Ad5MMP-1-infected, but not in Ad5LacZ-infected, @entity35 , the @entity82 was dramatically attenuated at 2 weeks after the infection. It is interesting to note that the number of activated hepatic stellate cells was also decreased in Ad5MMP-1-infected @entity35 . Moreover, disorganization of the hepatic trabecula, heterogeneity in the size of hepatocytes, and increased dried liver weight were observed only in Ad5MMP-1-treated @entity35 , suggesting that @entity1 @entity3334 stimulated hepatocyte proliferation, which was confirmed by @entity1603 staining. After 4 weeks, the proliferative effect of @entity1 @entity3334 almost disappeared, but the @entity1575 remained attenuated, whereas the @entity82 in Ad5LacZ-treated @entity35 persisted. Furthermore, the administration of Ad5MMP-1, but not Ad5LacZ, decreased type I collagen and generated a small collagen fragment in @entity1575 induced by bile duct ligation. CONCLUSIONS: Our findings show that transient @entity1 @entity3334 overexpression in the liver effectively attenuates established @entity82 and induces hepatocyte proliferation.
