Effects of TGF-beta s in the liver: cell proliferation and fibrogenesis.
Effects of TGF-beta s in the liver: cell proliferation and fibrogenesis.
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DOI：
10.1002/9780470514061.ch11
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发表时间：
1991
期刊：
影响因子：
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通讯作者：
Nelson Fausto;J. Mead;Phillip A. Gruppuso;Alberto Castilla;S. Jakowlew
中科院分区：
文献类型：
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作者：
Nelson Fausto;J. Mead;Phillip A. Gruppuso;Alberto Castilla;S. Jakowlew
TGF-β 1是体内和培养中肝细胞增殖的有效抑制剂，也是纤维化发生的诱导剂。它由正常、再生、肿瘤和肿瘤前肝脏中的非实质细胞产生。TGF-β 2和β 3也存在于肝脏非实质细胞中，其mRNA的量在肝脏再生过程中增加。TGF-β 2与TGF-β 1具有相似的作用。正常成年大鼠肝脏膜与TGF-β 1结合的动力学与单个高亲和力结合位点的存在一致;再生12-72小时的肝脏膜显示出在正常或假手术大鼠的肝脏中未检测到的高亲和力结合位点。来自正常和再生肝脏的膜的亲和标记显示两种受体蛋白，其Mr为85，000和65，000。相反，在培养的肝上皮细胞的膜制备物中检测到对应于Mr 280，000的结合蛋白的显著条带。虽然TGF-β 1受体的调节发生在肝再生过程中，但尚不可能确定哪种受体负责肝细胞中的TGF-β 1效应。其他研究已经证明了TGF-β 1 mRNA表达与慢性肝病患者纤维化的各种指标之间的显著相关性。因此，在动物和人类中，TGF-β 1似乎在慢性肝病纤维化的发病机制中起主要作用。
TGF-beta 1 is a potent inhibitor of hepatocyte proliferation in vivo and in culture and an inducer of fibrogenesis. It is produced by non-parenchymal cells in normal, regenerating, neoplastic and pre-neoplastic liver. TGF-beta 2 and beta 3 are also found in liver non-parenchymal cells and the amounts of their mRNAs increase during liver regeneration. TGF-beta 2 has similar effects to TGF-beta 1. Membranes from normal adult rat liver bind TGF-beta 1 with kinetics consistent with the presence of a single high affinity binding site; membranes from livers that have been regenerating for 12-72 hours show high affinity binding sites not detected in livers of normal or sham-operated rats. Affinity labelling of membranes from normal and regenerating liver shows two receptor proteins with Mr 85,000 and 65,000. In contrast, a prominent band corresponding to a binding protein of Mr 280,000 is detected in membrane preparations of cultured liver epithelial cells. Although modulation of TGF-beta 1 receptors occurs during liver regeneration, it has not been possible to determine which receptor is responsible for the TGF-beta 1 effects in hepatocytes. Other studies have demonstrated a significant correlation between TGF-beta 1 mRNA expression and various indicators of fibrogenesis in patients with chronic liver disease. Thus in animals and humans TGF-beta 1 appears to play a major role in the pathogenesis of fibrosis in chronic liver disease.