Czaja M J, Weiner F R, Flanders K C, Giambrone M A, Wind R, Biempica L, Zern M A
Albert Einstein College of Medicine, Marion Bessin Liver Research Center, Bronx, New York 10461.
J Cell Biol. 1989 Jun;108(6):2477-82. doi: 10.1083/jcb.108.6.2477.
Despite extensive efforts, little progress has been made in identifying the factors that induce hepatic fibrosis. Transforming growth factor-beta (TGF-beta) has been shown to enhance collagen production, therefore its role in hepatic fibrosis was investigated. Treatment of cultured hepatic cells with TGF-beta 1 increased type I procollagen mRNA levels 13-fold due to post-transcriptional gene regulation. When two animal models of hepatic fibrosis, murine schistosomiasis and CCl4-treated rats, were examined, they both exhibited increased levels of TGF-beta 1 gene expression at times that somewhat preceded the increase in collagen synthesis. In contrast, in murine schistosomiasis, mRNA levels of tumor necrosis factor and interleukin-1 peaked early in the fibrogenic process. Immunohistochemical analysis showed TGF-beta 1 to be present in normal mouse liver and to be markedly increased in mice infected with schistosomiasis. TGF-beta 1 appeared in the hepatic parenchyma, primarily in hepatocytes. These findings strongly suggest a role for TGF-beta 1 in a pathophysiological state.
尽管付出了巨大努力，但在确定诱发肝纤维化的因素方面进展甚微。已证明转化生长因子-β（TGF-β）可增强胶原蛋白的产生，因此对其在肝纤维化中的作用进行了研究。由于转录后基因调控，用TGF-β1处理培养的肝细胞可使I型前胶原mRNA水平提高13倍。当检查两种肝纤维化动物模型，即小鼠血吸虫病和CCl4处理的大鼠时，它们在胶原合成增加之前的某个时间均表现出TGF-β1基因表达水平升高。相比之下，在小鼠血吸虫病中，肿瘤坏死因子和白细胞介素-1的mRNA水平在纤维化过程早期达到峰值。免疫组织化学分析表明，TGF-β1存在于正常小鼠肝脏中，在感染血吸虫病的小鼠中明显增加。TGF-β1出现在肝实质中，主要在肝细胞中。这些发现有力地表明TGF-β1在病理生理状态中发挥作用。
