SPATIAL AND TEMPORAL PATTERNS OF GENE-EXPRESSION FOR THE PROTEOGLYCANS BIGLYCAN AND DECORIN AND FOR TRANSFORMING GROWTH-FACTOR-BETA-1 REVEALED BY IN-SITU HYBRIDIZATION DURING EXPERIMENTALLY-INDUCED LIVER FIBROSIS IN THE RAT

Expression of the proteoglycans biglycan and decorin and of transforming growth factor-beta1 at various stages of liver fibrosis induced experimentally in rats by oral administration of thioacetamide was examined. Using in situ hybridization combined with immunocytochemical staining for cell-type characteristic markers, we demonstrate spatial and temporal expression patterns specific for each of the genes. Biglycan gene expression levels coincided tightly with the activity and extent of fibrosis, fat-storing cells and their transformed form, the myofibroblast-like cells, being the major contributors. Decorin messenger RNA was detectable only after the transition to the chronic inflammatory stage in nonparenchymal cells of periportal fields and, transiently, in the forming septa. In the cirrhotic stage, expression was detected solely in periportal fields with enhanced bile duct proliferation. Transforming growth factor-beta1 expression was undetectable in normal liver. During the subacute inflammatory stage, a hepatocyte subpopulation expressing low levels of transforming growth factor-beta1 occurred at the limiting plate. With the progression of fibrosis, transforming growth factor-beta1 expression levels increased considerably but remained restricted to the mesenchymal cells of the fibrotic septa.