Suppression of transforming growth factor-β results in upregulation of transcription of regeneration factors after chronic liver injury
Suppression of transforming growth factor-β results in upregulation of transcription of regeneration factors after chronic liver injury
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DOI：
10.1016/j.jhep.2004.08.015
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发表时间：
2004-12-01
影响因子：
25.7
通讯作者：
Sata, M
中科院分区：
文献类型：
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作者：
Nakamura, T;Ueno, T;Sata, M
背景/目标：为探讨显性负性TGF-β受体表达对二甲基亚硝胺（DMN）诱导的大鼠肝损伤后肝再生的影响，采用DMN处理大鼠3周，然后静脉注射AdTbeta-TR、AdLacZ或生理盐水。采用免疫组化和TUNEL法检测肝细胞增殖和凋亡的变化。实时定量PCR和北方印迹法检测肝细胞再生因子（HGF、TGF-α、EGF、IGF-I）和IL-6的mRNA表达。在AdTbeta-TR治疗组中，EGF和IGF-I mRNA表达水平在基因转移后第1天显著升高，并持续3天，TGF-α mRNA表达水平在基因转移后第2 ~ 5天显著升高，HGF mRNA表达水平仅在基因转移后第2天显著上调，而TGF-α mRNA表达水平在基因转移后第3天显著升高。结论：抗TGF-β分子干预治疗DMN诱导的肝损伤大鼠，可促进肝细胞增殖，减少肝细胞凋亡，并上调多种生长因子的转录。(C)2004年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background/Aims: To determine the effects of dominant-negative TGF-beta receptor expression during liver regeneration in rats with dimethylnitrosamine (DMN)-induced liver injury.Methods: Rats were first treated with DMN for 3 weeks, and then intravenously injected once with AdTbeta-TR, AdLacZ, or saline. Serial changes in hepatocyte proliferation and apoptosis were evaluated by immunohistochemistry using anti-Ki67 antibody, and TUNEL staining, respectively. The mRNA expression of regeneration factors (HGF, TGF-alpha, EGF, and IGF-I) and IL-6 were evaluated by real-time PCR and northern blotting.Results: Anti-TGF-beta molecular intervention up-regulated hepatocyte proliferation and inhibited apoptosis. In the AdTbeta-TR-treated rats, EGF and IGF-I mRNA expression levels were significantly increased at day 1 and remained high for 3 days after gene transfer; TGF-alpha mRNA expression levels were significantly increased at 2 to 5 days after gene transfer; HGF mRNA expression levels were significantly up-regulated at day 2 only after gene transfer; while IL-6 mRNA expression level tended to increase at day 1, but decreased thereafter.Conclusions: In rats with DMN-induced liver injury, anti-TGF-beta molecular intervention therapy stimulates proliferation and reduces apoptosis of hepatocytes, and also up-regulates the transcription of various growth factors. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.