Wnt信号通路与肝纤维化发生发展的关系

赵东康; 骆伟伟; 余水平

doi:10.3969/j.issn.1001-5256.2018.11.033

Wnt信号通路与肝纤维化发生发展的关系

DOI: 10.3969/j.issn.1001-5256.2018.11.033

1. 桂林医学院
2. 广西医科大学附属第一医院肝胆外科二病区

基金项目:

广西医疗卫生适宜技术研究与开发项目(S201536)；

详细信息

中图分类号: R575.2
计量
- 文章访问数: 1391
- HTML全文浏览量: 55
- PDF下载量: 351
- 被引次数: 0
出版历程
- 出版日期: 2018-11-20

Role of the Wnt signaling pathway in the development and progression of liver fibrosis

Research funding:

摘要

摘要: 肝纤维化的发生发展机制复杂,包含众多细胞内外信号转导通路,但其具体机制尚未明确。最近较多研究证实Wnt信号通路异常激活进而使肝星状细胞活化是导致肝纤维化的重要原因;靶向抑制Wnt信号通路能够阻止肝星状细胞的活化、增殖,从而达到抗纤维化的目的。对Wnt信号通路在肝纤维化发生和发展中的作用以及干扰Wnt信号通路抗肝纤维化的最新研究进展进行综述,期望为抗肝纤维化和延缓早期肝硬化提供新的思路。
- 肝硬化 /
- 脂细胞 /
- 信号传导 /
- 综述
Abstract: Liver fibrosis has a complex pathogenesis and involves various intracellular and extracellular signal transduction pathways, but its specific pathogenesis remains unclear. Recent studies have confirmed that the activation of hepatic stellate cells due to abnormal activation of the Wnt signaling pathway is an important cause of liver fibrosis, and targeted inhibition of the Wnt signaling pathway can prevent the activation and proliferation of hepatic stellate cells and thus achieve an antifibrogenic effect. This article reviews the role of the Wnt signaling pathway in the development and progression of liver fibrosis and the latest research advances in the antifibrogenic effect of the interference of the Wnt signaling pathway, in order to provide new ideas for anti-hepatic fibrosis and the delay of early-stage cirrhosis.
- liver cirrhosis /
- adipocytes /
- signal transduction /
- review

HTML全文

参考文献(32)

[1]SCHON HT, BARTNECK M, BORKHAM-KAMPHORST E, et al.Pharmacological intervention in hepatic stellate cell activation and hepatic fibrosis[J].Front pharmacol, 2016, 7:33-55.

[2]ZHOU XL, YU SP.Role of Wnt signaling pathway in progression of liver cirrhosis[J].J Clin Hepatol, 2015, 31 (9) :1540-1542. (in Chinese) 周雪玲, 余水平.Wnt信号通路对肝硬化进展的影响[J].临床肝胆病杂志, 2015, 31 (9) :1540-1542.

[3]LEE Y, LEE JK, AHN SH, et al.Wnt signaling in glioblastoma and therapeutic opportunities[J].Lab Invest, 2016, 96 (2) :137-150.

[4]ZHAN T, RINDTORFF N, BOUTROS M.Wnt signaling in cancer[J].Oncogene, 2017, 36 (11) :1461-1473.

[5]GUI XY, SHI HF, CHEN YX.Function of the noncanonical Wnt pathway during bone development and metabolism[J].Chin J Exp Surg, 2017, 34 (8) :1437-1440. (in Chinese) 桂雪洋, 施鸿飞, 陈一心.非经典Wnt信号通路在骨发育和骨代谢中的作用[J].中华实验外科杂志, 2017, 34 (8) :1437-1440.

[6]WETTERE AJV, LAW JM, HINTON DE, et al.Anchoring hepatic gene expression with development of fibrosis and neoplasia in a toxicant-induced fish model of liver injury[J].Toxicologic Pathology, 2013, 41 (5) :744-760.

[7] AKHMETSHINA A, PALUMBO K, DEES C, et al.Activation of canonical Wnt signalling is required for TGF-β-mediated fibrosis[J].Nat Commun, 2012, 3:735-747.

[8]BAARSMA HA, HOEKE A, SPANJER, et al.Activation of Wnt/beta-catenin signaling in pulmonary fibroblasts by TGF-beta (1) is increased in chronic obstructive pulmonary disease[J].PLo S One, 2011, 6 (9) :e25450.

[9]TIAN X, ZHANG J, TAN TK, et al.Association ofβ-catenin with P-Smad3 but not LEF-1 dissociates in vitro profibrotic from anti-inflammatory effects of TGF-β1[J].J Cell Sci, 2013, 126 (1) :67-76.

[10]LABBE, LETAMENDIA A, ATTISANO L.Association of Smads with lymphoid enhancer binding factor 1/T cell-specific factor mediates cooperative signaling by the transforming growth factor-beta and Wnt pathways[J].Proc Natl Acad Sci U S A, 2000, 97 (15) :8358-8363.

[11]GAO C, CHEN YG.Dishevelled:The hub of Wnt signaling[J].Cell Signal, 2010, 22 (5) :717-727.

[12]TULI R, TULI S, NANDI S, et al.Transforming growth factorbeta-mediated chondrogenesis of human mesenchymal progenitor cells involves N-cadherin and mitogen-activated protein kinase and Wnt signaling cross-talk[J].J Biol Chem, 2003, 278 (42) :41227-41237.

[13]GUO X, RAMIREZ A, WADDELL DS, et al.Axin and GSK3-control Smad3 protein stability and modulate TGF-signaling[J].Gene Dev, 2008, 22 (1) :106-120.

[14]RASHID ST, HUMPHRIES JD, BYRON A, et al.Proteomic analysis of extracellular matrix from the hepatic stellate cell line LX-2identifies CYR61 and Wnt-5a as novel constituents of fibrotic liver[J].J Proteome Res, 2012, 11 (8) :4052-4064.

[15]LAU LF.CCN1/CYR61:The very model of a modern matricellular protein[J].Cell Mol Life Sci, 2011, 68 (19) :3149-3163.

[16]LI ZQ, DING W, SUN SJ, et al.Cyr61/CCN1 is regulated by Wnt/β-catenin signaling and plays an important role in the progression of hepatocellular carcinoma[J].PLo S One, 2012, 7 (4) :e35754.

[17]XIONG WJ, HU LJ, JIAN YC, et al.Wnt5a participates in hepatic stellate cell activation observed by gene expression profile and functional assays[J].World J Gastroenterol, 2012, 18 (15) :1745-1752.

[18]CRUCIAT CM, NIEHRS C.Secreted and transmembrane Wnt inhibitors and activators[J].Cold Spring Harb Perspect Biol, 2013, 5 (3) :a015081.

[19]YANAGIDA A, IWAISAKO K, HATANO E, et al.Downregulation of the Wnt antagonist Dkk2 links the loss of Sept4 and myofibroblastic transformation of hepatic stellate cells[J].Biochim Biophys Acta, 2011, 1812 (11) :1403-1411.

[20]XIAO C, WANG L, ZHU L, et al.Secreted frizzled-related protein 2 is epigenetically silenced and functions as a tumor suppressor in oral squamous cell carcinoma[J].Mol Med Rep, 2014, 10 (5) :2293-2298.

[21]XAVIER CP, MELIKOVA M, CHUMAN Y, et al.Secreted Frizzledrelated protein potentiation versus inhibition of Wnt3a/β-catenin signaling[J].Cell Signal, 2014, 26 (1) :94-101.

[22]KIM J, KIM S.In silico identification of sfrp1 as a hypermethylated gene in colorectal cancers[J].Genomics Inform, 2014, 12 (4) :171-180.

[23]ZHANG Y, YU X, WANG Z, et al.Pokeweed antiviral protein attenuates liver fibrosis in mice through regulating Wnt/Jnk mediated glucose metabolism[J].Saudi J Gastroenterol, 2018, 24 (3) :157.

[24]AKCORA B, STORM G, BANSAL R.Inhibition of canonical WNT signaling pathway byβ-catenin/CBP inhibitor ICG-001 ameliorates liver fibrosis in vivo through suppression of stromal CX-CL12[J].Biochim Biophys Acta, 2018, 1864 (3) :804-818.

[25]ZHAO Q, QIN CY, ZHAO ZH, et al.Epigenetic modifications in hepatic stellate cells contribute to liver fibrosis[J].Tohoku J Exp Med, 2013, 229 (1) :35-43.

[26]ZHU NL, WANG J, TSUKAMOTO H.The Necdin-Wnt pathway causes epigenetic peroxisome proliferator-activated receptor gamma repression in hepatic stellate cells[J].J Biol Chem, 2010, 285 (40) :30463-30471.

[27]VALLE A, LECARPENTIER Y, GUILLEVIN R, et al.Interactions between TGF-β1, canonical WNT/β-catenin pathway and PPARγin radiation-induced fibrosis[J].Oncotarget, 2017, 8 (52) :90579-90604.

[28]ZHANG F, LU S, HE J, et al.Ligand activation of PPARγby ligustrazine suppresses pericyte functions of hepatic stellate cells via SMRT-mediated transrepression of HIF-1α[J].Theranostics, 2018, 8 (3) :610-626.

[29]HASAN HF, ABDEL-RAFEI MK, GALAL SM.Diosmin attenuates radiation-induced hepatic fibrosis via boosting PPAR-γexpression and hampering mi R-17-5p activated canonical Wnt/β-catenin signaling[J].Biochem Cell Biol, 2017, 95 (3) :400-414.

[30]YEDID N, KALMA Y, MALCOV M, et al.The effect of a germline mutation in the APC gene onβ-catenin in human embryonic stem cells[J].BMC cancer, 2016, 16 (1) :95T2.

[31]SUN X, HE Y, MA TT, et al.Participation of mi R-200a in TGF-β1-mediated hepatic stellate cell activation[J].Mol Cell Biochem, 2014, 388 (1-2) :11-23.

[32]MA ZG, LV XD, ZHAN LL, et al.Human urokinase-type plasminogen activator gene-modified bone marrow-derived mesenchymal stem cells attenuate liver fibrosis in rats by down-regulating the Wnt signaling pathway[J].World J Gastroenterol, 2016, 22 (6) :2092-2103.

施引文献

资源附件(0)

访问统计