Effect of uncoupling protein 2 on activation of hepatic stellate cell in liver fibrosis of rats

doi:10.3969/j.issn.0529-1356.2014.04.008

Abstract

Abstract:

Objective To explore the role of uncoupling protein 2 (UCP2) in the development of hepatic fibrosis and its molecular mechanism. Methods The CCl4-induced liver fibrosis rat modelin vivo was established to observe the pathological changes of rat livers. The expression levels of UCP2 and p38 mitogen activated protein kinase (p38 MAPK） were detected by using the techniques of Western blotting, Real-time PCR and immunohistochemistry. The hepatic stellate cells (HSC) were stimulated by CCl4 and UCP2-specific inhibitor Genipin to mimic liver fibrosis in vitro. The expression levels of UCP2 and p38MAPK were determined by using Western blotting. Results We found that UCP2 and α-SMA expression levels increased significantly (P<0.05, n=10) in the liver of rats with CCl4-induced liver fibrosis when compared with that of the normal control rats in vivo. Similarly, the expression levels of UCP2 and p38 MAPK were up regulated (P<0.05, n=6) in CCl4-treated HSC cells in vitro. However, the expressions of UCP2 and p38 MAPK were down regulated (P<0.05, n=6) in genipin-treated HSC cells in vitro. Conclusion UCP2 is involved in liver fibrosis, and probably contributed to the activation and proliferation of hepatic stellate cells.

Key words: Uncoupling protein 2, Liver fibrosis, Hepatic stellate cells, p38 Mitogen activated protein kinase, Western blotting, Rat

AN Jian-duo JIANG Ying BAI Yun-fei WANG Xue-jiang*. Effect of uncoupling protein 2 on activation of hepatic stellate cell in liver fibrosis of rats[J]. AAS, 2014, 45(4): 480-484.

References

［1］Huang Y，Huang Ch，Li J.Effect of cytokines secreted from Kupffer cell on HSC proliferation, apoptosis in hepatic fibrosis process［J］.Chinese Pharmacological Bulletin,2010,26（1）：9-13.(in Chinese)
黄艳,黄成,李俊. 肝纤维化病程中Kupffer细胞分泌的细胞因子对肝星状细胞活化增殖、凋亡的调控［J］. 中国药理学通报,2010,26（1）:9-13.
［2］Wang Y1, Jiang XY, Liu L,et al.Phosphatidylinositol 3-kinase/Akt pathway regulates hepatic stellate cell apoptosis［J］. World J Gastroenterol, 2008,14(33):5186-5191.
［3］An JD,Jiang Y.UCP2 and cancer［J］.Progress in Physiological Sciences,2013,44(3):233-236. (in Chinese)
安建多,江瑛. 线粒体解耦联蛋白UCP2与恶性肿瘤［J］. 生理科学进展,2013,44(3):233-236.
［4］Krauss S，Zhang CY，Lowell BB.The mitochondrial uncoupling-protein homologues［J］. Nat Rev Mol Cell Biol，2005，6(3)：248-261.
［5］Pecqueur C，Alves Guerra MC，Gelly C，et al.Uncoupling protein 2，in vivo distribution，induction upon oxidative stress，and evidence for translational regulation［J］.J Biol Chem，2001，276(12)：8705-8712.
［6］Wang Z, Xu JP, Zheng YC,et al.Peroxisome proliferator-activated receptor gamma inhibits hepatic fibrosis in rats［J］. Hepatobiliary Pancreat Dis Int, 2011, 10(1):64-71.
［7］Wang HB, Fan HN, Deng Y.The research progress of hepatic stellate cells and liver fibrosis［J］.Journal of Qinghai Medical College, 2008, 29(2):133-137. (in Chinese)
王宏宾,樊海宁,邓勇.肝星形细胞与肝纤维化的研究进展［J］.青海医学院学报,2008,29(2):133-137. 
［8］Li CY, Li YL.Effects of extracellular matrix on expression of MMP-2,TIMPs and MT1-MMP of hepatic stellate cells［J］.Chinese Journal of Modern Applied Pharmacy,2008,25(5):389-393. (in Chinese)
李从岩,李一雷. 细胞外基质成分对肝星形细胞MMP-2、TIMPs和MT1-MMP表达的影响［J］. 中国现代应用药学,2008,25(5):389-393.
［9］Wang Q, Guan XQ, Luo K.Influence of vitamin E and selenium on UCP2 and other correlation factors in non-alcoholic fatty liver of rats［J］.Zoological Research， 2008,29(1):37-42. (in Chinese)
王倩，管小琴，罗凯.维生素E和硒对大鼠非酒精性脂肪性肝病解耦联蛋白2及相关因子表达的影响［J］. 动物学研究，2008,29(1):37-42.
［10］Hu XX, Wang Y, Wang N.Effect of p38MAPK,NF-κB and oxidative stress in liver fibrosis［J］.Chinese Journal of Public Health,2013,29(6):834-836. (in Chinese)
胡晓霞,王艳,王妮.p38MAPK、NF-κB与氧化应激在肝纤维化中作用［J］.中国公共卫生,2013,29(6):834-836.

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