Immunophenotypical Changes of Myofibroblasts Appearing in Thioacetamide-Induced Hepatic Fibrosis in Rats

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Myofibroblasts play important roles in hepatic fibrosis through the production of extracellular matrix. The cells are derived mainly from hepatic stellate cells (HSCs). Immunoexpression of cytoskeletons such as vimentin, desmin, α-smooth muscle action (α-SMA) and glial fibrillary acidic protein (GFAP) was analyzed in myofibroblasts appearing in acute type hepatic fibrosis (AHF; 300 mg/kg, a single injection) and chronic type hepatic fibrosis (CHF; 100 mg/kg, twice a week for 10 weeks), which were both induced in F344 rats by thioacetamide. In AHF, the number of vimentin-and desmin-positive cells showed the highest levels on day 3 after the injection, in conformity with an increased number of α-SMA-positive myofibroblasts, whereas that of GFAP-positive cells reached a plateau as early as day 1. In CHF, α-SMA- and desmin-positive myofibroblasts showed similar kinetics to each other. The numbers gradually increased from weeks 1 to 7 and then expanded quickly at week 10 when pseudolobules were completely developed. On the other hand, the number of vimentin- and GFAP-positive cells in CHF slightly increased at weeks 3 and 4, respectively, and then decreased until week 10. Interestingly, the greatest expression number among these cytoskeletons was vimentin in AHF, whereas it was desmin in CHF. The present study showed that myofibroblasts express various cytoskeletons, and that there is a difference in the expression patterns between AHF and CHF. By RT-PCR, nerve growth factor (NGF) mRNA expression markedly increased with time in both AHF and CHF, suggesting that NGF might participate in development of hepatic fibrosis by regulating HSCs with its receptor.
日本毒性病理学会の論文
2004-12-30

Immunophenotypical Changes of Myofibroblasts Appearing in Thioacetamide-Induced Hepatic Fibrosis in Rats

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