Effect of some peroxisome proliferators on transforming growth factor-beta 1 gene expression and insulin-like growth factor II/mannose-6-phosphate receptor gene expression in rat liver.

Male Sprague-Dawley rats were given daily oral doses of either corn oil (control), 80 mg/kg nafenopin (NAF), 50 mg/kg methylclofenapate (MCP), 50 mg/kg Wy-14,643 (WY) or 250 mg/kg clofibric acid (CA) for 7 days. All four compounds increased relative liver weight and produced hepatic peroxisome proliferation as assessed by induction of both peroxisomal (palmitoyl-CoA oxidation) and microsomal (lauric acid 12-hydroxylase) fatty acid oxidising enzyme activities. RNA was extracted from liver samples and analysed for expression of transforming growth factor-beta 1 (TGF-beta 1) and the insulin-like growth factor II/mannose-6-phosphate (IGFII/Man6P) receptor (which may be involved in transporting latent TGF-beta 1 into hepatocytes). TGF-beta 1 mRNA levels were increased to 151-178% of control by all four compounds, whereas NAF, MCP and WY, but not CA, increased IGFII/Man6P receptor mRNA levels to 195-209% of control. The induction of TGF-beta 1 and IGFII/Man6P receptor expression by short term treatment with peroxisome proliferators may represent an adaptive response to limit the initial hyperplastic effects of such compounds.