UV Irradiation Activates JNK and Increases αI(I) Collagen Gene Expression in Rat Hepatic Stellate Cells

摘要: Hepatic stellate cells (HSCs) become activated into myofibroblast-like during the early stages of hepatic injury associated with fibrogenesis. The subsequent dysregulation αI(I) collagen gene expression is a central pathogenetic step development cirrhosis. Our recent study in rat HSCs (Davis, B. H., Chen, A., and Beno, D. (1996) J. Biol. Chem. 271, 11039–11042) found that ERK1,2 activation might be required for maximal expression. However, role parallel JNK cascade regulating was unknown. In this study, we initially UV irradiation but not ERK1,2. Furthermore, increased endogenous α I(I) mRNA abundance stimulated transcription HSCs. effect Jun on further evaluated via transfection chloramphenicol acetyltransferase reporter plasmids various sizes truncated 5′ upstream promoter sequence (UPS) gene. This revealed dominant negative factor JUN suppressed maintained media 20% serum constitutively cultured 0.4% serum. utilized distal GC box 5′-UPS to regulate transcription. observation confirmed by site-directed mutagenesis. co-transfection experiments, col-chloramphenicol mutagenized dn-JUN or irradiation. Southwestern blotting analyses gel shift assays basic element-binding protein antiserum suggested bound protein, recently described DNA-binding protein. conclusion, current combined our previous report suggests cascades through different regions may play receiving extracellular signals pathway.