OPG/RANKL/RANK信号通路在非酒精性脂肪性肝病进展中的作用

向照; 杨晋辉

doi:10.3969/j.issn.1001-5256.2020.07.040

OPG/RANKL/RANK信号通路在非酒精性脂肪性肝病进展中的作用

DOI: 10.3969/j.issn.1001-5256.2020.07.040

向照,
杨晋辉

昆明医科大学第二附属医院消化内科

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中图分类号: R575.5
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出版历程
- 出版日期: 2020-07-20

Role of the OPG/RANKL/RANK signaling pathway in the progression of nonalcoholic fatty liver disease

Department of Gastroenterology, The Second Affiliated Hospital of Kunming Medical University, Kunming 650000, China

摘要

摘要:
非酒精性脂肪性肝病（NAFLD）已成为全球范围内最常见的肝脏疾病,在现有基础上更好诊断、治疗NAFLD也愈发迫切。骨保护素（OPG）/NF-κB受体活化因子（RANKL）/NF-κB受体活化因子受体（RANK）信号通路是参与骨代谢平衡的重要信号通路。分别介绍了OPG、RANKL、RANK及OPG/RANKL/RANK系统,简述了OPG/RANKL/RANK信号通路通过激活NF-κB调节炎症因子生成,促使NAFLD发展的研究现状。指出OPG/RANKL/RANK系统可作为NAFLD治疗的潜在新靶点。
- 非酒精性脂肪性肝病 /
- 骨保护素 /
- NF-κB /
- 信号传导
Abstract:
Nonalcoholic fatty liver disease( NAFLD) has now become the most common liver disease around the world,and there is an urgent need for better diagnosis and treatment of NAFLD. The osteoprotegerin( OPG)/receptor activator of nuclear factor-kappa B ligand( RANKL)/receptor activator of nuclear factor-kappa B( RANK) signaling pathway is an important signaling pathway involved in the balance of bone metabolism. This article introduces the OPG,RANKL,RANK,and OPG/RANKL/RANK systems and elaborates on the current research on the role of the OPG/RANKL/RANK signaling pathway in regulating the production of inflammatory factors and promoting the progression of NAFLD by activating NF-κB. It is pointed out that the OPG/RANKL/RANK system may be used as a potential target for the treatment of NAFLD.
- non-alcoholic fatty liver disease /
- osteoprotegerin /
- NF-kappa B /
- signal transduction

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参考文献(29)

[1]COTTER TG,RINELLA M.NAFLD 2020:The state of the disease[J].Gastroenterology,2020.[Online ahead of print]

[2]ADAMS LA,ROBERTS SK,STRASSER SI,et al.Nonalcoholic fatty liver disease burden:Australia,2019-2030[J].Gastroenterol Hepatol,2020.[Online ahead of print]

[3]JIANG YZ,NIE HM,WANG R.Pathogenesis of non-alcoholic fatty liver disease[J].J Clin Hepatol,2019,35(11):2588-2591.(in Chinese)姜煜资，聂红明，汪蓉．非酒精性脂肪性肝病的发病机制[J]．临床肝胆病杂志，2019,35(11):2588-2591．

[4]PACIFICO L,ANDREOLI GM,D'AVANZO M,et al.Role of osteoprotegerin/receptor activator of nuclear factor kappa B/receptor activator of nuclear factor kappa B ligand axis in nonalcoholic fatty liver disease[J].World J Gastroenterol,2018,24(19):2073-2082．

[5]LIU W,ZHANG X.Receptor activator of nuclear factor-κB ligand(RANKL)/RANK/osteoprotegerin system in bone and other tissues(review)[J].Mol Med Rep,2015,11(5):3212-3218．

[6]WONG BR,RHO J,ARRON J,et al.TRANCE is a novel ligand of the tumor necrosis factor receptor family that activates c-Jun N-terminal kinase in T cells[J].J Biol Chem,1997,272(40):25190-25194．

[7]LACEY DL,TIMMS E,TAN HL,et al.Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation[J].Cell,1998,93(2):165-176．

[8]KARTSOGIANNIS V,ZHOU H,HORWOOD NJ,et al.Localization of RANKL(receptor activator of NF kappa B ligand)mRNA and protein in skeletal and extraskeletal tissues[J].Bone,1999,25(5):525-534．

[9]ANDERSON DM,MARASKOVSKY E,BILLINGSLEY WL,et al.Ahomologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function[J].Nature,1997,390(6656):175-179．

[10]DARNAY BG,HARIDAS V,NI J,et al.Characterization of the intracellular domain of receptor activator of NF-kappa B(RANK).Interaction with tumor necrosis factor receptor-associated factors and activation of NF-kappab and c-Jun N-terminal kinase[J].J Biol Chem,1998,273(32):20551-20555．

[11]DARNAY BG,NI J,MOORE PA,et al.Activation of NF-kappa Bby RANK requires tumor necrosis factor receptor-associated factor(TRAF)6 and NF-kappa B-inducing kinase.Identification of a novel TRAF6 interaction motif[J].J Biol Chem,1999,274(12):7724-7731．

[12]HSU H,LACEY DL,DUNSTAN CR,et al.Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand[J].Proc Natl Acad Sci U SA,1999,96(7):3540-3545．

[13]ONO T,HAYASHI M,SASAKI F,et al.RANKL biology:Bone metabolism,the immune system,and beyond[J].Inflamm Regen,2020,40:2．

[14]CHEN JY,WANG C,WANG J,et al.Research progress of MAPKsignal pathway[J].China Med Pharm,2011,1(8):42-44.(in Chinese)陈建勇，王聪，王娟，等．MAPK信号通路研究进展[J]．中国医药科学，2011,1(8):42-44．

[15]ZHANG B,LI M,ZOU Y,et al.Corrigendum:NF-κB/orai1 facilitates endoplasmic reticulum stress by oxidative stress in the pathogenesis of non-alcoholic fatty liver disease[J].Front Cell Dev Biol,2019,7:290．

[16]YANG L,WANG Z,JIANG L,et al.Total flavonoids extracted from oxytropis falcata bunge improve insulin resistance through regulation on the IKKβ/NF-κB inflammatory pathway[J].Evid Based Complement Alternat Med,2017,2017:2405124．

[17]KIL IS,KIM SY,PARK JW.Glutathionylation regulates Ikappa B[J].Biochem Biophys Res Commun,2008,373(1):169-173．

[18]WANG WQ,YI WC,LIN YH.Human umbilical cord mesenchymal stem cells alleviate liver damage of non-alcoholic fatty liver disease rats by inhibiting TLR4/NF-κB and oxidative stress[J/CD].Chin JCell Stem Cell(Electronic Edition),2018,8(5):297-302.(in Chinese)王文清，易文城，林拥华．脐带间充质干细胞介导TLR4/NF-κB炎症通路及氧化应激改善NAFLD大鼠肝脏损伤作用研究[J/CD]．中华细胞与干细胞杂志(电子版)，2018,8(5):297-302．

[19]KUMAR RAJENDRAN N,GEORGE BP,CHANDRAN R,et al.The Influence of Light on Reactive Oxygen Species and NF-кB in Disease Progression[J].Antioxidants(Basel),2019,8(12):640．

[20]MUSSO G,CASSADER M,GAMBINO R.Non-alcoholic steatohepatitis:Emerging molecular targets and therapeutic strategies[J].Nat Rev Drug Discov,2016,15(4):249-274．

[21]CHEN J,MONTAGNER A,TAN NS,et al.Insights into the Role of PPARβ/δin NAFLD[J].Int J Mol Sci,2018,19(7):1893．

[22]NEUSCHWANDER-TETRI BA.Therapeutic landscape for NAFLD in2020[J].Gastroenterology,2020,158(7):1984-1998.e3．

[23]EMERY JG,MCDONNELL P,BURKE MB,et al.Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL[J].J Biol Chem,1998,273(23):14363-14367．

[24]ZHANG C,LUO X,CHEN J,et al.Osteoprotegerin promotes liver steatosis by targeting the ERK-PPAR-γ-CD36 Pathway[J].Diabetes,2019,68(10):1902-1914．

[25]MARUYAMA K,TAKADA Y,RAY N,et al.Receptor activator of NF-kappa B ligand and osteoprotegerin regulate proinflammatory cytokine production in mice[J].J Immunol,2006,177(6):3799-3805．

[26]METRAKOS P,NILSSON T.Non-alcoholic fatty liver disease-a chronic disease of the 21~(st)century[J].J Biomed Res,2018,32(5):15-23．

[27]MANTOVANI A,SANI E,FASSIO A,et al.Association between non-alcoholic fatty liver disease and bone turnover biomarkers in post-menopausal women with type 2 diabetes[J].Diabetes Metab,2019,45(4):347-355．

[28]TAKENO A,YAMAMOTO M,NOTSU M,et al.Administration of anti-receptor activator of nuclear factor-kappa B ligand(RANKL)antibody for the treatment of osteoporosis was associated with amelioration of hepatitis in a female patient with growth hormone deficiency:Acase report[J].BMC Endocr Disord,2016,16(1):66．

[29]HAO YL,BIAN ZL,JU LL,et al.RANK/RANKL acts as a protective factor by targeting cholangiocytes in primary biliary cholangitis[J].Dig Dis Sci,2020,65(2):470-479.

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