Research advances in the role of autophagy in liver cells and regulation of MAPK pathway
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摘要: 自噬是真核生物细胞内一种高度保守的细胞程序,在肝脏的营养和能量代谢中起着重要作用。促进肝细胞自噬,可保护细胞应对外界不良刺激,但若自噬过度,可以引起肝细胞自噬性细胞死亡。肝星状细胞(HSC)是肝纤维化发生、发展过程中一种重要细胞,自噬可为其活化提供能量,但也可能导致其死亡。简述了自噬与肝细胞、HSC的关系;介绍了近年来丝裂原活化蛋白激酶通路与自噬的关系,提出了深入研究肝纤维化过程中自噬与调节通路间的关系,可为研发抗肝纤维化药物提供新靶标的观点。Abstract: Autophagy is a highly conservative cellular process in eukaryotes that plays an important role in nutrition and energy metabolism in the liver. It can promote the autophagy of hepatocytes and protect the hepatocytes against the adverse external stimulation,but excessive autophagy can cause autophagic cell death of hepatocytes. Hepatic stellate cells( HSC) play an important role in the development and progression of liver fibrosis. Autophagy can provide energy for their activation,but may also lead to their death. This article introduces the relationship of autophagy with hepatocytes / HSC and the mitogen- activated protein kinase pathway,and points out that in- depth studies on the relationship between autophagy and pathway regulation during liver fibrosis can provide new targets for developing antifibrotic drugs.
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Key words:
- autophagy /
- liver cirrhosis /
- hepatocytes /
- hepatic stellate cells /
- mitogen-activated protein kinase /
- review
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[1] RAVIKUMAR B,SARKAR S,DAVIES JE,et al.Regulation of mammalian autophagy in physiology and pathophysiology[J].Physiol Rev,2010,90(4):1383-1435. [2]JIANG PD,MIZUSHIMA N.Autophagy and human diseases[J].Cell Res,2014,24(1):69-79. [3] YANG ZF,KLIONSKY DJ.Eaten alive:a history of macroautophagy[J].Nature cell biology,2010,12(9):814-822. [4]FU MY,HE YJ,LYU X,et al.Transforming growth factorbeta1reduces apoptosis via autophagy activation in hepatic stellate cells[J].Mol Med Rep,2014,10(3):1282-1288. [5]DENG J,HUANG Q,WANG YQ,et al.Hypoxia-inducible factor-1alpha regulates autophagy to activate hepatic stellate cells[J].Biochem Biophys Res Commun,2014,454(2):328-334. [6]HAO H,ZHANG D,SHI J,et al.Sorafenib induces autophagic cell death and apoptosis in hepatic stellate cell through the JNK and Akt signaling pathways[J].Anticancer Drugs,2016,27(3):192-203. [7]LIU XY,HE YJ,YANG QH,et al.Induction of autophagy and apoptosis by miR-148a through the sonic hedgehog signaling pathway in hepatic stellate cells[J].Am J Cancer Res,2015,5(9):2569-2589. [8]GROSSINI E,BELLOFATTO K,FARRUGGIO S,et al.Levosimendan inhibits peroxidation in hepatocytes by modulating apoptosis/autophagy interplay[J].PLoS One,2015,10(4):e0124742. [9]CAI N,ZHAO X,JING YY,et al.Autophagy protects against palmitate-induced apoptosis in hepatocytes[J].Cell Biosci,2014,4(1):28. [10]LI ST,LI JX,SHEN C,et al.tert-Butylhydroquinone(tB HQ)protects hepatocytes against lipotoxicity via inducing autophagy independently of Nrf2 activation[J].Biochim Biophys Acta,2014,1841(1):22-33. [11]ZHANG Y,CHEN ML,ZHOU Y,et al.Resveratrol improves hepatic steatosis by inducing autophagy through the cA MP signaling pathway[J].Mol Nutr Food Res,2015,59(8):1443-1457. [12]JUNG TW,HONG HC,HWANG HJ,et al.C1q/TNF-Related Protein 9(CTRP9)attenuates hepatic steatosis via the autophagymediated inhibition of endoplasmic reticulum stress[J].Mol Cell Endocrinol,2015,417:131-140. [13]ZHANG YJ,ZHENG NR,LIU B,et al.Sodium nitrite reduces lipid accumulation in steatotic cells by enhancing autophagy[J].Acta Pharmaceutica Sinica,2015,50(8):1000-1007.(in Chinese)张优敬,郑乃汭,刘彬,等.亚硝酸钠增强自噬减轻肝脂肪变性的细胞脂肪蓄积[J].药学学报,2015,50(8):1000-1007. [14]JI GY,WANG YQ,DENG YX,et al.Resveratrol ameliorates hepatic steatosis and inflammation in methionine/choline-deficient diet-induced steatohepatitis through regulating autophagy[J].Lipids Health Dis,2015,14(1):134. [15]ILYAS G,ZHAO EP,LIU K,et al.Macrophage autophagy limits acute toxic liver injury in mice through down regulation of interleukin-1beta[J].J Hepatol,2016,64(1):118-127. [16]LUO MX,WONG SH,CHAN MT,et al.Autophagy mediates HBx-induced nuclear factor-kappaB activation and release of IL-6,IL-8,and CXCL2 in hepatocytes[J].J Cell Physiol,2015,230(10):2382-2389. [17]WU Y,ZHANG Y,WANG L,et al.The role of autophagy in kidney inflammatory injury via the NF-κB route induced by LPS[J].Int J Med Sci,2015,12(8):655-667. [18]BAULIES A,RIBAS V,NUNEZ S,et al.Lysosomal cholesterol accumulation sensitizes to acetaminophen hepatotoxicity by impairing mitophagy[J].Sci Rep,2015,5:18017. [19]CHEN C,DENG MH,SUN Q,et al.Lipopolysaccharide stimulates p62-dependent autophagy-like aggregate clearance in hepatocytes[J].Biomed Res Int,2014,2014(1):267350. [20]DANGI A,HUANG C,TANDON A,et al.Endotoxin-stimulated rat hepatic stellate cells induce autophagy in hepatocytes as a survival mechanism[J].J Cell Physiol,2016,231(1):94-105. [21]BAENA M,SANGUESA G,HUTTER N,et al.Fructose supplementation impairs rat liver autophagy through mT ORC activation without inducing endoplasmic reticulum stress[J].Biochim Biophys Acta,2015,1851(2):107-116. [22]WEBBER JL,TOOZE SA.Coordinated regulation of autophagy by p38alpha MAPK through mA tg9 and p38IP[J].EMBO J,2010,29(1):27-40. [23]WU DF,CEDERBAUM AI.Inhibition of autophagy promotes CYP2E1-dependent toxicity in Hep G2 cells via elevated oxidative stress,mitochondria dysfunction and activation of p38 and JNK MAPK[J].Redox Biol,2013,1(1):552-565. [24]ZHANG L,NIU WX,HE ZJ,et al.Autophagy suppression by exercise pretreatment and p38 inhibition is neuroprotective in cerebral ischemia[J].Brain Res,2014,1587(4):127-132. [25]ZHONG W,ZHU HC,SHENG FG,et al.Activation of the MAPK11/12/13/14(p38 MAPK)pathway regulates the transcription of autophagy genes in response to oxidative stress induced by a novel copper complex in HeL a cells[J].Autophagy,2014,10(7):1285-1300. [26]MORUNO-MANCHON JF,PEREZ-JIMENEZ E,KNECHT E.Glucose induces autophagy under starvation conditions by a p38MAPK-dependent pathway[J].Biochem J,2013,449(2):497-506. [27]HERNANDEZ-GEA V,HILSCHER M,ROZENFELD R,et al.Endoplasmic reticulum stress induces fibrogenic activity in hepatic stellate cells through autophagy[J].J Hepatol,2013,59(1):98-104. [28]XIAO YZ,LIU H,YU JJ,et al.Activation of ERK1/2 ameliorates liver steatosis in lepin receptor deficient(db/db)mice via stimulating ATG7-dependent autophagy[J].Diabetes,2016,65(2):393-405. [29]AKIN D,WANG SK,HABIBZADEGAH-TARI P,et al.A novel ATG4B antagonist inhibits autophagy and has a negative impact on osteosarcoma tumors[J].Autophagy,2014,10(11):2021-2035. [30]MARTINEZ-LOPEZ N,ATHONVARANGKUL D,MISHALL P,et al.Autophagy proteins regulate ERK phosphorylation[J].Nat commun,2013,4(7):2799. [31]GU XD,WANG Y,XIANG JB,et al.Interferon-γtriggers hepatic stellate cell-mediated immune regulation through MEK/ERK signaling pathway[J].Clin Dev Immunol,2013,2013:389807. [32]FANG L,ZHAN SX,HUANG C,et al.TRPM7 channel regulates PDGF-BB-induced proliferation of hepatic stellate cells via PI3K and ERK pathways[J].Toxicol Appl Pharmacol,2013,272(3):713-725. [33]LI XM,WANG XL,HAN CY,et al.Astragaloside IV suppresses collagen production of activated hepatic stellate cells via oxidative stress-mediated p38 MAPK pathway[J].Free Radic Biol Med,2013,60:168-176.
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