Armendariz-Borunda J, Seyer J M, Kang A H, Raghow R
Veterans Administration Medical Center, Memphis, Tennessee 38104.
FASEB J. 1990 Feb 1;4(2):215-21. doi: 10.1096/fasebj.4.2.2298342.
Transforming growth factor beta (TGF beta) has been implicated as having a central role in the postinflammatory tissue regeneration and fibrosis. To test its potential involvement in events that follow hepatotoxin-mediated liver regeneration and fibrosis, we quantitated changes in the steady-state levels of TGF beta mRNA in parenchymal and nonparenchymal cells at various times after an acute treatment with CCl4, and also compared TGF beta gene expression in these two cell types from livers subjected to chronic CCl4 treatment. The parenchymal and nonparenchymal cells from normal liver contained undetectable amounts of TGF beta mRNA. In contrast, we could readily detect TGF beta specific transcripts in both the parenchymal and nonparenchymal cells after acute injury. Nonparenchymal cells from acutely injured liver contained fivefold greater amounts of TGF beta mRNA, which peaked at 48 h and declined thereafter. In chronically treated rat livers (1, 2, 3, and 7 wk after the initiation of CCl4 treatment), increased expression of TGF beta mRNA was found only in nonparenchymal cells obtained after 2-3 wk of treatment. Strikingly large elevations in the steady-state levels of beta-actin mRNA in CCl4-treated liver were also observed, which may be related to the known regenerative processes associated with acute liver toxicity. Changing dynamics of TGF beta gene expression, therefore, appear to be an important attribute of regenerating liver after acute or chronic CCl4 toxicity.
转化生长因子β（TGFβ）被认为在炎症后组织再生和纤维化过程中起核心作用。为了测试其在肝毒素介导的肝脏再生和纤维化后续事件中的潜在作用，我们在急性给予四氯化碳（CCl4）处理后的不同时间，定量分析了实质细胞和非实质细胞中TGFβ mRNA稳态水平的变化，并比较了慢性CCl4处理的肝脏中这两种细胞类型的TGFβ基因表达。正常肝脏的实质细胞和非实质细胞中未检测到TGFβ mRNA。相反，急性损伤后，我们在实质细胞和非实质细胞中都能轻易检测到TGFβ特异性转录本。急性损伤肝脏的非实质细胞中TGFβ mRNA含量高出五倍，在48小时达到峰值，随后下降。在慢性处理的大鼠肝脏中（CCl4处理开始后1、2、3和7周），仅在处理2 - 3周后获得的非实质细胞中发现TGFβ mRNA表达增加。在CCl4处理的肝脏中还观察到β-肌动蛋白mRNA稳态水平显著升高，这可能与已知的急性肝毒性相关的再生过程有关。因此，TGFβ基因表达的动态变化似乎是急性或慢性CCl4毒性后肝脏再生的一个重要特征。
