EXPRESSION OF PLATELET-DERIVED GROWTH-FACTOR AND ITS RECEPTORS IN NORMAL HUMAN LIVER AND DURING ACTIVE HEPATIC FIBROGENESIS

Expression of platelet-derived growth factor (PDGF) and its receptor ( R) subunits was evaluated in normal human liver and in cirrhotic liver tissue by in situ hybridization and immunohistochemistry, In normal l iver, PDGF and PDGF-R subunit expression was limited to a few mesenchy mal cells of the portal tract stroma and vessels, lit cirrhotic liver, PDGF-A and -B chain mRNA expression was markedly increased and was co -distributed with immunoreactivity for PDGF-AA and -BB in infiltrating inflammatory cells and along vascular structures within fibrous septa , These aspects were paralleled by a mark;ed overexpression of PDGF-R alpha- and beta-subunit mRNAs and of the relative immunoreactivities i n a wide range of mesenchymal cells in fibrous septa and in perisinuso idal alpha-smooth-muscle-actin-positive cells. In general, expression and distribution of PDGF-R subunits appeared to be related to the acti vation of different mesenchymal cell types involved in the fibroprolif erative process, Therefore, we evaluated the expression of PDGF-R subu nits in liver tissue specimens with increasing degrees of necroinflamm atory activity, The results of this additional study confirmed that ex pression of PDGF-R subunits is highly correlated with the severity of histological lesions and collagen deposition, Our results, providing e vidence for a functional involvement of PDGF/PDGF-R in liver fibrogene sis, greatly support the results of previous in vitro studies and dire ct attention toward pharmacological strategies able to affect the seri es of signaling events arising from the autophosphorylation of PDGF-R subunits.