Human hepatic lipocytes synthesize tissue inhibitor of metalloproteinases-1. Implications for regulation of matrix degradation in liver.

摘要: Hepatic lipocytes play a central role in the pathogenesis of liver fibrosis, both via production extracellular matrix proteins and through secretion metalloproteinases. In this study, we have characterized lipocyte expression release tissue inhibitor metalloproteinases-1 (TIMP-1), an important metalloproteinase activity, whose has not previously been examined. TIMP-1 was immunolocalized to human lipocytes, confirmed by ELISA culture media; (mean +/- SD) 159 79 ng TIMP-1/10(6) cells per 24 h. Evidence for functional inhibitory activity released obtained (a) reverse zymography that demonstrated single band, M(r) 28 kD, co-migrated with TIMP-1-positive control sample; (b) unmasking inhibited gelatinase medium separating it from using gelatin sepharose chromatography; chromatographed increased more than 20-fold, compared unfractionated medium, could be reinhibited adding back fractions contained inhibitor. By Northern analysis, freshly isolated exhibited low levels mRNA TIMP-1, but markedly relative beta-actin activation during cell culture. We conclude hepatic synthesize potent inhibitor, increases activation. These data indicate can regulate degradation liver, suggest activated may contribute progression fibrosis.