7-19]。 MAPK信号通路可以通过对肝星状细胞活化、增殖、凋亡的调控参与肝纤维化的形成。炎症反应、氧化应激、细胞因子等不同的刺激因素作用于肝星状细胞的相关受体激活了MAPK信号通路中的ERK、JNK两大信号途径,现研究表明它们对HSC的激活是正性调节,但至肝纤维化逆转录过程中,H-ras、A-raf.MAPKK2、ERK1,表达水平明显升高[20]。
5 展 望
肝纤维化是继发于肝脏炎症或损伤后修复过程中的炎症反应,ECM在肝内过量沉积,最终导致肝硬化。肝纤维化的形成机制非常复杂,确切机制尚不清楚。MAPK信号通路是肝纤维化形成的重要通路之一,MAPK信号通路与肝纤维化的发生有着密切的关系, MAPK信号通路中的ERK、JNK、P38MAPK三大信号途径与HSC之间的相互作用关系至今还不明确。ERK、JNK通路倾向是对肝星状细胞的活化和增值为正向调节,加剧了肝纤维化的形成。P38MAPK信号对肝星状细胞的调节还不明确有待进一步证实。随着对MAPK信号通路理解的不断深入, 其在肝纤维化发生的分子机制中的作用会越来越多地引起人们的关注。
【参考文献】
[1]Zhang Y,Dong C,et al.Regulatory mechanisms of mitogen-activated kinase signaling[J].Cell Mol Life Sci,2007,64(21):2771-2789.
[2]Nishimoto S.Nishida E,et al.MAPK signalling :ERK5 versus ERK1/2[J].EMB0Rep,2006,7(8):782-786.
[3]Cao Q,Mak KM,Lieber CS,et al.Leptin enhances alpha1(I) collagen gene expression in LX-2 human hepatic stellate cells through JAK-mediated H2O2-dependent MAPK pathways[J].Cell Biochem,2006,97(1):188-197.
[4]Liou GY,Zhang H,Miller EM,et al. Induced, selective proteolysis of MLK3 negatively regulates MLK3-JNK signaling[J].Biochem J,2010 Feb 16.
[5]Deng ZY,Li J,Jin Y,et al. Effect of oxymatrine on the p38 mitogen-activated protein kinases signalling pathway in rats with CCl4 induced hepatic fibrosis[J].Chin Med J (Engl),2009,122(12):1449-1454.
[6]Jameel NM ,Thirunaukkarasu C ,Watkins SC,et al. p38-MAPK- and caspase-3-mediated superoxide-induced apoptosis of rat hepatic stellate cells: reversal by retinoic acid [J].Cell physiol,2009,218(1):157-166.
[7]McCaw BJ,Chow SY,Wong ES,et al.Identification and characterization of mErk5-T.a novel Erk5/Bmkl splice variant[J].Gene,2005,345(2):183-190.
[8]Gressner AM,Bachem MC.Molecular mechanisms of liver fibrogenesis-a homage to the role of activated fat-storing cells[J].Digestion,1995,56(5):335-346.
[9]Tsukada S,Parsons C J,Rippe R A ,et al.Mechanisms of liver fibrosis[J].Clinica Chimica Acta,2006,364(1-2):33-60.
[10]TA
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