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 transformi ng growth factor-beta1 at various stages of liver fibrosis induced exp erimentally in rats by oral administration of thioacetamide was examin ed. Using in situ hybridization combined with immunocytochemical stain ing for cell-type characteristic markers, we demonstrate spatial and t emporal expression patterns specific for each of the genes. Biglycan g ene expression levels coincided tightly with the activity and extent o f fibrosis, fat-storing cells and their transformed form, the myofibro blast-like cells, being the major contributors. Decorin messenger RNA was detectable only after the transition to the chronic inflammatory s tage in nonparenchymal cells of periportal fields and, transiently, in the forming septa. In the cirrhotic stage, expression was detected so lely in periportal fields with enhanced bile duct proliferation. Trans forming growth factor-beta1 expression was undetectable in normal live r. 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 gro wth factor-beta1 expression levels increased considerably but remained restricted to the mesenchymal cells of the fibrotic septa.