Transgenic overexpression of steroid sulfatase alleviates cholestasis

作     者：Mengxi Jiang Meishu Xu Songrong Ren Kyle W.Selcer Wen Xie Mengxi Jiang;Meishu Xu;Songrong Ren;Kyle W.Selcer;Wen Xie

作者机构：Center for PharmacogeneticsDepartment of Pharmaceutical SciencesUniversity of PittsburghPittsburghPAUSA Department of Biological SciencesDuquesne UniversityPittsburghPAUSA Department of Pharmacology&Chemical BiologyUniversity of PittsburghPittsburghPAUSA 

出 版 物：《Liver Research》 (肝脏研究（英文）)

年 卷 期：2017年第1卷第1期

页      面：63-69页

学科分类：081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 070303[理学-有机化学] 0703[理学-化学] 

基　　金：This work was supported in part by the National Institutes of Health grants DK083952 and HD073070(to W.X.) 

主　　题：Steroid sulfatase Bile acid Toxicity Cholestasis Liver X receptor 

摘      要：Background and Aim:Sulfotransferase(SULT)-mediated sulfation and steroid sulfatase(STS)-mediated desulfation represent two critical mechanisms that regulate the chemical and functional homeostasis of endogenous and exogenous *** catalyzes the hydrolysis of steroid sulfates to form *** cholesterol derivative oxysterols are known to be endogenous ligands of the liver X receptor(LXR),a nuclear receptor with anti-cholestasis activity,whereas the sulfated oxysterols antagonize LXR *** conversion of sulfated oxysterols to their non-sulfated counterparts is catalyzed by *** aim of this study is to determine whether STS can alleviate cholestasis by increasing the activity of ***:Liver-specific STS transgenic mice were created and subject to the lithocholic acid(LCA)-induced model of ***:Transgenic overexpression of STS in the liver promoted bile acid elimination and alleviated LCAinduced *** protective effect of the STS transgene was associated with the activation of LXR and induction of LXR target genes,likely because of the increased conversion of the antagonistic oxysterol sulfates to the agonistic ***:STS has a novel function in controlling the homeostasis of bile acids by regulating endogenous LXR ligands.