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

Male Sprague-Dawley rats were given daily oral doses of eithercorn 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 liverweight and produced hepatic peroxisome proliferation as assessedby induction of both peroxisomal (palmitoyl-CoA oxidation) andmicrosomal (lauric acid 12-hydroxylase) fatty acid oxidisingenzyme activities. RNA was extracted from liver samples andanalysed for expression of transforming growth factor-ß₁(TGF-ß₁) and the insulin-like growth factor II/mannose-6-phosphate(IGFII/Man6P) receptor (which may be involved in transportinglatent TGF-ß₁, into hepatocytes). TGF-ß₁mRNA levels were increased to 151 –178% of control byall four compounds, whereas NAF, MCP and WY, but not CA, increasedIGFII/Man6P receptor mRNA levels to 195–209% of control.The induction of TGF-ß₁ and IGFII/Man6P receptor expressionby short term treatment with peroxisome proliferators may representan adaptive response to limit the initial hyperplastic effectsof such compounds.