肝星状细胞的激活与凋亡相关信号通路研究进展(3)
综上所述，HSCs发生激活和凋亡的机制非常复杂，涉及的信号途径很多，目前单一的信号通路已经很难解释清楚HSCs激活与凋亡的机制，为此以后研究HSCs激活与凋亡的信号通路之间的相互作用已成为热点。另外还有Fas/FasL途径，神经生长因子途径，粘附分子途径，线粒体途径和活性氧途径等参与了HSCs的激活与凋亡。如研究发现在HSCs活化过程中CD95(Fas)及其配体CD95L(FasL)表达显著增加,CD95拮抗抗体能完全阻断正常和已进入凋亡周期HSCs的凋亡[42]。总之，从以上论述可以看出，C/EBPs通路和PPAR通路为核内基因表达变化进而对HSC产生影响，而TGF-β/Smad通路、NF-κB通路、JAK/STAT通路、PI3K通路和MAPK通路等均需通过细胞膜受体与配体结合，影响胞质区分子结构和功能，然后转入核内调控基因表达。面对如此多相关的机制，仍然需要不断的深入研究HSCs发生激活和凋亡的信号通路机制及多种信号通路之间相互调节的机制，从而寻找到合适的HSCs分子靶点，为靶向HSCs而防治肝纤维化的治疗提供坚实的理论基础。
, http://www.100md.com
参考文献
[1]Kordes C,Sawitza I,Haussinger D.Hepatic and pancreatic stellate cells in focus.Biol Chem.2009,390(10):1003-1012.
[2]Atzori L,Poli G,Perra A.Hepatic stellate cell:a star cell in the liver.Int J Biochem Cell Biol,2009,41(8-9):1639-1642.
[3]Novo E,di Bonzo LV,Cannito S,Colombatto S,Parola M.Hepatic myofibroblasts:a heterogeneous population of multifunctional cells in liver fibrogenesis.Int J Biochem Cell Biol,2009,41(11):2089-2093.
, 百拇医药
[4]Friedman SL.Molecular regulation of hepatic fibrosis,an integrated cellular response to tissue injury.J Biol Chem,2000,275(4):2247-2250.
[5]IredaleJP.Hepatic stellate cell behavior during resolution of liver injury.Semin Liver Dis,2001,(21):427-436.
[6]Pizani M,Marra F.Cytokine receptors and signaling in hepatic stellate cells.Semin Liver Dis,2001,(21):397-416.
[7]Canbay A,Taimr P,Torok N,et al.Apoptotic body engulfment by a human stellate cell line is profibrogenic.Lab Invest,2003,83(5):655-663.
, 百拇医药
[8]Saile B,KnittelT,MatthesN,et al.CD95/CD95L-mediated apoptosis of the hepatic stellate cell.A mechanism terminating uncontrolled hepatic stellate cell proliferation during hepatic tissue repair.Am J Pathol,1997,151(5):1265-1272.
[9]Uyama N,Shimahara Y,Okuyama H,et al.Carbenoxlone inhibits DNA synthesis and collagen gene expression in rat hepatic stellate cells in culture.J Hepatol,2003,5(39):749-755.
[10]Saile B,DeRocco P,Dudas J,et al.IGF-I induces DNA syn-thesis and apoptosis in rat liver hepatic stellate cells(HSC)but DNA synthesis and proliferation in rat liver myofibroblasts(rMF).LabInvest,2004,(84):1037-1049.
, 百拇医药
[11]Issa R, Zhou X,Constandinou CM, et al.Spontaneous recovery from micronodular cirrhosis:evidence for incomplete resolution associated with matrix cross-linking.Gastroenterology,2004,126(7):1795-1808.
[12]Gressner AM,Weiskirchen R,Breitkopf K,etal.Roles of TGF-beta in hepatic fibrosis.Front Biosci，2002,(7):793-807.
[13]Derynck R,Zhang YE.Smad-dependent and Smad-independent pathways in TGF-beta family signalling.Nature，2003，425(6958):577-584.
, 百拇医药
[14]Chen YW,Li DG,Wu JX,et al.Tetrandrine inhibits activation of rat hepatic stellate cells stimulated by transforming growth factor-beta in vitro via up-regulation of Smad 7.J Ethnopharmaco,2005,100(3):299-305.
[15]Schnabl B,Kweon YO,Frederick JP,et al.The role of Smad3 in mediating mouse hepatic stellate cell activation.Hepatology,2001,34(1):89-100.
[16]Tahashi Y,Matsuzaki K,Date M,et al.Differential regulation of TGF-beta signal in hepatic stellate cells between acute and chronic rat liver injury.Hepatology,2002,35(1):49-61., 百拇医药(尤俊勇 王效民)
, http://www.100md.com
参考文献
[1]Kordes C,Sawitza I,Haussinger D.Hepatic and pancreatic stellate cells in focus.Biol Chem.2009,390(10):1003-1012.
[2]Atzori L,Poli G,Perra A.Hepatic stellate cell:a star cell in the liver.Int J Biochem Cell Biol,2009,41(8-9):1639-1642.
[3]Novo E,di Bonzo LV,Cannito S,Colombatto S,Parola M.Hepatic myofibroblasts:a heterogeneous population of multifunctional cells in liver fibrogenesis.Int J Biochem Cell Biol,2009,41(11):2089-2093.
, 百拇医药
[4]Friedman SL.Molecular regulation of hepatic fibrosis,an integrated cellular response to tissue injury.J Biol Chem,2000,275(4):2247-2250.
[5]IredaleJP.Hepatic stellate cell behavior during resolution of liver injury.Semin Liver Dis,2001,(21):427-436.
[6]Pizani M,Marra F.Cytokine receptors and signaling in hepatic stellate cells.Semin Liver Dis,2001,(21):397-416.
[7]Canbay A,Taimr P,Torok N,et al.Apoptotic body engulfment by a human stellate cell line is profibrogenic.Lab Invest,2003,83(5):655-663.
, 百拇医药
[8]Saile B,KnittelT,MatthesN,et al.CD95/CD95L-mediated apoptosis of the hepatic stellate cell.A mechanism terminating uncontrolled hepatic stellate cell proliferation during hepatic tissue repair.Am J Pathol,1997,151(5):1265-1272.
[9]Uyama N,Shimahara Y,Okuyama H,et al.Carbenoxlone inhibits DNA synthesis and collagen gene expression in rat hepatic stellate cells in culture.J Hepatol,2003,5(39):749-755.
[10]Saile B,DeRocco P,Dudas J,et al.IGF-I induces DNA syn-thesis and apoptosis in rat liver hepatic stellate cells(HSC)but DNA synthesis and proliferation in rat liver myofibroblasts(rMF).LabInvest,2004,(84):1037-1049.
, 百拇医药
[11]Issa R, Zhou X,Constandinou CM, et al.Spontaneous recovery from micronodular cirrhosis:evidence for incomplete resolution associated with matrix cross-linking.Gastroenterology,2004,126(7):1795-1808.
[12]Gressner AM,Weiskirchen R,Breitkopf K,etal.Roles of TGF-beta in hepatic fibrosis.Front Biosci，2002,(7):793-807.
[13]Derynck R,Zhang YE.Smad-dependent and Smad-independent pathways in TGF-beta family signalling.Nature，2003，425(6958):577-584.
, 百拇医药
[14]Chen YW,Li DG,Wu JX,et al.Tetrandrine inhibits activation of rat hepatic stellate cells stimulated by transforming growth factor-beta in vitro via up-regulation of Smad 7.J Ethnopharmaco,2005,100(3):299-305.
[15]Schnabl B,Kweon YO,Frederick JP,et al.The role of Smad3 in mediating mouse hepatic stellate cell activation.Hepatology,2001,34(1):89-100.
[16]Tahashi Y,Matsuzaki K,Date M,et al.Differential regulation of TGF-beta signal in hepatic stellate cells between acute and chronic rat liver injury.Hepatology,2002,35(1):49-61., 百拇医药(尤俊勇 王效民)