Role of transforming growth factor beta type II receptor in hepatic fibrosis: studies of human chronic hepatitis C and experimental fibrosis in rats.
Role of transforming growth factor beta type II receptor in hepatic fibrosis: studies of human chronic hepatitis C and experimental fibrosis in rats.
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发表时间：
1999
期刊：
影响因子：
13.5
通讯作者：
D. Roulot;A. Sevcsik;T. Coste;A. Strosberg;S. Marullo
中科院分区：
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作者：
D. Roulot;A. Sevcsik;T. Coste;A. Strosberg;S. Marullo
转化生长因子β（TGF-β）是一种抗增殖和促纤维化的细胞因子，通过由I型和II型（TbetaRII）组分组成的受体发出信号。我们研究了肝损伤过程中TbetaRII表达的变化，并将其与TGF-β 1的抗增殖和促纤维化作用相关联。实验材料包括慢性丙型肝炎患者和结扎胆总管引起肝损伤的大鼠的肝活检样品。从正常或损伤的大鼠肝脏中分离星状细胞，并作为新鲜分离物进行研究。在患者的活检样本中，使用竞争性反向聚合酶链反应（PCR）测量TGF-β 1和TbetaRII的mRNA。与健康对照组相比，慢性丙型肝炎患者TGF-β 1 mRNA显著升高（P = 0.03），而TbetaRII mRNA显著降低（P = 0.001）。在大鼠模型中，胆管结扎后5天，TGF-β表达增加，星形细胞中TbetaRII的mRNA是对照肝脏星形细胞中TbetaRII mRNA的40%。这与I型胶原mRNA表达增加和星状细胞增殖相一致。TGF-β和II型受体表达之间的相互关系表明配体介导的受体下调。TbetaRII水平的降低似乎允许增殖，同时支持正在进行的纤维化。我们的结论是，这种受体的调制可能是至关重要的伤口修复在肝脏的进展。
Transforming growth factor beta (TGF-beta) is an antiproliferative and profibrogenic cytokine that signals through a receptor consisting of type I and type II (TbetaRII) components. We have examined changes in the expression of TbetaRII during liver injury, correlating this with the antiproliferative and profibrogenic effects of TGF-beta1. The experimental material consisted of biopsy samples of liver from patients with chronic hepatitis C and rats in which liver injury was induced by ligation of the common bile duct. Stellate cells were isolated from normal or injured rat liver and studied as fresh isolates. In the biopsy samples from patients, mRNAs for TGF-beta1 and TbetaRII were measured using competitive reverse polymerase chain reaction (PCR). TGF-beta1 mRNA was significantly increased in chronic hepatitis C relative to healthy controls (P =.03), while TbetaRII mRNA was significantly decreased (P =.001). In the rat model, 5 days after bile duct ligation during increased TGF-beta expression, mRNA for TbetaRII in stellate cells was 40% of that in stellate cells from control livers. This coincided with increased expression of collagen I mRNA and proliferation of stellate cells. The reciprocal relationship between expression of TGF-beta and the type II receptor suggest ligand-mediated receptor down-regulation. The decreased level of TbetaRII appears to be permissive for proliferation while supporting ongoing fibrogenesis. We conclude that modulation of this receptor may be critical to the progression of wound repair in liver.