Targeting the Wnt Signaling Pathway in Liver Fibrosis for Drug Options:An Update

查看全文 作　　者：Kristina [1,2]Duspara;Kristina [3,4,5]Bojanic;Josipa Ivanusic [2]Pejic;Lucija [1,2]Kuna;Tea Omanovic [1,2]Kolaric;Vjera [1,2]Nincevic;Robert [6,7,8]Smolic;Aleksandar [6,7,8]Vcev;Marija [9]Glasnovic;Ines Bilic [1,2,10]Curcic;Martina [1,2]Smolic

机构地区：[1]Department of Pharmacology and Biochemistry,Faculty of Dental Medicine and Health Osijek,J.J.Strossmayer University of Osijek,Osijek,Croatia;[2]Department of Pharmacology,Faculty of Medicine Osijek,J.J.Strossmayer University of Osijek,Osijek,Croatia;[3]Department of Biophysics and Radiology,Faculty of Dental Medicine and Health Osijek,J.J.Strossmayer University of Osijek,Osijek,Croatia;[4]Department of Biophysics and Radiology,Faculty of Medicine Osijek,J.J.Strossmayer University of Osijek,Osijek,Croatia;[5]Department of Radiology,Health Center Osijek,Osijek,Croatia;[6]Department of Medi-cine,Division of Gastroenterology/Hepatology,University Hospital Osijek,Osijek,Croatia;[7]Department of Pathophysiology,Physiology and Immunology,Faculty of Dental Medicine and Health Osijek,J.J.Strossmayer University of Osijek,Osijek,Croatia;[8]Department of Pathophysiology,Faculty of Medicine Osijek,J.J.Strossmayer University of Osijek,Osijek,Croatia;[9]Department of Medicine,Family Medicine and History of Medicine,Faculty of Medicine Osijek,J.J.Strossmayer University of Osijek,Osijek,Croatia;[10]Department of Medicine,Division of Endocrinology,University Hospital Osijek,Osijek,Croatia

出　　处：《Journal of Clinical and Translational Hepatology》索引2021年第9卷第6期,共12页

基　　金：the Croatian Ministry of Science and Education dedicated to multi-year institutional funding of scientific activity at the J.J.Strossmayer University of Osijek,Osijek,Croatia(grant numbers IP-2019-MEFOS-10(to MS)and IP7-2019-FDMZ(to MS)). 摘　　要：morbidity and mortality for healthcare systems worldwide.It imparts an enormous economic burden to societies,making continuous research and informational updates about its pathogenesis and treatment crucial.This review′s focus is on the current knowledge about the Wnt signaling path-way,serving as an important pathway in liver fibrosis development and activation of hepatic stellate cells(HSCs).Two types of Wnt pathways are distinguished,namely the ß-catenin-dependent canonical and non-canonical Ca^(2+) or planar cell polarity(PCP)-dependent pathway.The dynamic balance of physiologically healthy liver and hepatocytes is disturbed by repeated liver injuries.Activation of theß-catenin Wnt pathway prevents the regeneration of hepatocytes by the replacement of extracellular matrix(ECM),leading to the appearance of scar tissue and the formation of regenerated nodular hepatocytes,lacking the original function of healthy hepatocytes.Therefore,liver function is reduced due to the severely advanced disease.Selective inhibition ofß-catenin inhibits inflammatory processes(since chemokines and pro-inflammatory cytokines are produced during Wnt activation),reduces growth of activated HSCs and reduces collagen synthesis and angiogenesis,thereby reducing the progression of liver fibrosis in vivo.While the canonical Wnt pathway is usually inactive in a physiologically healthy liver,it shows activity during cell regeneration or renewal and in certain pathophysiological conditions,such as liver diseases and cancer.Targeted blocking of some of the basic components of the Wnt path-way is a therapeutic approach.These include the frizzled transmembrane receptor(Fz)receptors using the secreted frizzled-related protein family(sFRP),Fz-coreceptors low-density LRP 5/6 through dickkopf-related protein 1(DKK1)or niclosamide,glycogen kinase-3 beta(GSK-3β)using SB-216763,cyclic-AMP response element-binding protein(CBP)using PRI-724 and ICG-001,the lymphoid enhancer binding factor(LEF)/T cell-specific transcription factor(TCF)system as well as Wnt inhibitory factor 1(WIF1)and miR-17-5p using pinostilbene hydrate(PSH).Significant progress has been made in inhibiting Wnt and thus stopping the progression of liver fibrosis by diminishing key components for its action.Comprehending the role of the Wnt signaling pathway in liver fibrosis may lead to discovery of novel targets in liver fibrosis therapeutic strategies’development. 关键词：Liver fibrosis Wnt signaling pathway Hepatic stellate cell Therapeutic solutions

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Targeting the Wnt Signaling Pathway in Liver Fibrosis for Drug Options:An Update

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