A role for tissue transglutaminase in hepatic injury and fibrogenesis, and its regulation by NF-kappa B
A role for tissue transglutaminase in hepatic injury and fibrogenesis, and its regulation by NF-kappa B
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DOI：
10.1152/ajpgi.1997.272.2.g281
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发表时间：
1997-02-01
影响因子：
4.5
通讯作者：
Zern, MA
中科院分区：
文献类型：
--
作者：
Mirza, A;Liu, SL;Zern, MA
本研究旨在阐明组织转谷氨酰胺酶 (tTG)（一种催化蛋白质交联的酶）在肝纤维形成中的可能作用。在肝损伤和纤维形成的不同阶段，用CCl4溶液处理大鼠，然后将其处死。肝脏 tTG mRNA 水平早在第一次注射后 6 小时就显着增加，在 4 天和 1 周达到峰值，并在 8 周内保持增加。用 CCl4 处理的大鼠肝脏中 tTG 的酶活性增加，其方式与 Northern 印迹结果相似。细胞分离实验表明所有肝细胞类型均合成 tTG mRNA。在经 CCl4 处理的样品制备的核提取物中发现与 tTG 启动子的核因子 kappa B (NF-kappa B) 基序的结合增加。这些数据表明，肝损伤和纤维化期间 tTG 基因表达增加，表明该酶在肝纤维发生期间稳定纤维化带方面可能发挥作用。此外，NF-κB与tTG启动子的结合增加可能代表细胞损伤诱导tTG转录并因此增强纤维发生过程的机制之一。
This study was undertaken to delineate a possible role for tissue transglutaminase (tTG), an enzyme that catalyzes protein cross-linking, in hepatic fibrogenesis. Rats were treated with CCl4 solution and then killed at different stages of liver injury and fibrogenesis. Liver tTG mRNA levels were markedly increased as early as 6 h after the first injection, peaked at 4 days and 1 wk, and remained increased for 8 wk. The enzymatic activity of tTG was increased in livers of rats treated with CCl4, in a fashion that paralleled the Northern blot results. Cell isolation experiments indicated that all hepatic cell types synthesize tTG mRNA. Increased binding to the nuclear factor-kappa B (NF-kappa B) motif of the tTG promoter was found in the nuclear extracts prepared from CCl4-treated samples. These data demonstrate an increase in tTG gene expression during hepatic injury and fibrosis, suggesting a possible role for this enzyme in stabilizing the fibrotic bands during hepatic fibrogenesis. Moreover, increased NF-KB binding to the tTG promoter may represent one of the mechanisms by which cell injury induces tTG transcription and thus potentiates the process of fibrogenesis.