EXPRESSION OF PLATELET-DERIVED GROWTH-FACTOR IN A MODEL OF ACUTE LIVER-INJURY

Platelet-derived growth factor has been shown to play an important role in the repair process after acute tissue injury and in the pathogenesis of several fibrogenic disorders. The aim of this study was to evaluate whether increased expression of platelet-derived growth factor and its P-receptor subunit occurs in a model of acute liver injury. Male Sprague-Dawley rats were given a single intragastric dose of carbon tetrachloride and killed at intervals of 24, 48 and 72 hr and 1. wk. Control animals were included in each group. Platelet derived growth factor-B chain mRNA expression, analyzed by RNase protection assay, was not detectable in control samples or in samples obtained 24 hr br 1 wk after carbon tetrachloride. However, the presence of protected fragments of 130 kb was clearly detected after 48 hr and was still present, although less abundant, after 72 hr. The distribution of platelet-derived growth factor protein in liver tissue sections, evaluated by immunohistochemistry, was restricted to centrilobular veins and portal tracts in normal liver. In carbon tetrachloride-treated rats, prominent staining was observed in areas corresponding to hepatocellular necrosis and inflammatory infiltration. This feature, already present at 24 hr after carbon tetrachloride, became more marked at 48 hr with a gradual resolution after 72 hr. The expression of platelet-derived growth factor-receptor beta-subunit mRNA, evaluated by in situ hybridization, was markedly increased after carbon tetrachloride with a peak at 24 hr and was mainly localized over mesenchymal cells in the hepatic sinusoids. The overall analysis of these results suggests that platelet-derived growth factor may play a positive role in the process of tissue repair after acute liver injury by promoting effective necrotic tissue removal and the reconstruction of an adequate extracellular matrix network.