Fausto N, Mead J E, Gruppuso P A, Castilla A, Jakowlew S B
Department of Pathology, Brown University, Providence, RI 02912.
Ciba Found Symp. 1991;157:165-74; discussion 174-7. doi: 10.1002/9780470514061.ch11.
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.
转化生长因子β1（TGF-β1）在体内和体外培养中都是肝细胞增殖的强效抑制剂，也是纤维生成的诱导剂。它由正常、再生、肿瘤性和癌前肝脏中的非实质细胞产生。TGF-β2和β3也存在于肝脏非实质细胞中，并且在肝脏再生过程中它们的mRNA含量增加。TGF-β2具有与TGF-β1相似的作用。正常成年大鼠肝脏的膜以与单一高亲和力结合位点存在相一致的动力学结合TGF-β1；再生12 - 72小时的肝脏的膜显示出正常或假手术大鼠肝脏中未检测到的高亲和力结合位点。正常和再生肝脏膜的亲和标记显示出两种分子量分别为85,000和65,000的受体蛋白。相比之下，在培养的肝上皮细胞的膜制剂中检测到一条对应于分子量为280,000的结合蛋白的显著条带。虽然在肝脏再生过程中TGF-β1受体发生了调节，但尚无法确定哪种受体负责TGF-β1在肝细胞中的作用。其他研究表明，慢性肝病患者中TGF-β1 mRNA表达与各种纤维生成指标之间存在显著相关性。因此，在动物和人类中，TGF-β1似乎在慢性肝病纤维化的发病机制中起主要作用。
