Bile acids evoke placental inflammation by activating Gpbar1/NF-κB pathway in intrahepatic cholestasis of pregnancy

作     者：YouHua Zhang YouDong Pan ChangDong Lin YaJuan Zheng Hao Sun HaiLong Zhang JunLei Wang MengYa Yuan Tao Duan QiaoLing Du JianFeng Chen 

作者机构：State Key Laboratory of Cell BiologyCAS Center for Excellence in Molecular Cell ScienceInstitute of Biochemistry and Cell BiologyShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200031China Department of ObstetricsShanghai First Maternity and Infant HospitalTongji University School of MedicineShanghai 200040China 

出 版 物：《Journal of Molecular Cell Biology》 (分子细胞生物学报（英文版）)

年 卷 期：2016年第8卷第6期

页      面：530-541页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：supported by grants from the 973 Program(2014CB541905) the National Natural Science Foundation of China(31525016,31471309,31190061) Personalized Medicines-Molecular Signature-based Drug Discovery and Development,the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA12000000) the Science and Technology Commission of Shanghai Municipality(11JC1414200),SKLCB(KF2012002) the CAS/SAFEA International Partnership Program for Creative Research Teams 

主　　题：fetal outcome G protein-coupled receptor maternal cholestasis placental inflammation ursodeoxycholic acid 

摘      要：Intrahepatic cholestasis of pregnancy(ICP)is a cholestatic disorder with potentially deleterious consequences for *** a clear correlation between the elevated levels of maternal serum bile acids and deficient fetal outcome has been established in clinical practice,the underlying mechanisms remain ***,we report that bile acids induce NF-κB pathway activation via G protein-coupled bile acid receptor 1(Gpbar1),with consequent upregulation of inflammatory genes in trophoblasts,leading to aberrant leukocyte infiltration and inflammation in *** acid(UDCA),a drug used clinically to treat ICP,competes with other bile acids for binding with Gpbar1 and thus inhibits bile acid-induced inflammatory response in trophoblasts and improves fetal survival in pregnant rats with obstructive ***,inhibition of NF-κB by andrographolide is more effective than UDCA in benefiting placentas and ***,anti-inflammation therapy targeting Gpbar1/NF-κB pathway could be effective in suppressing bile acid-induced inflammation and alleviating ICP-associated fetal disorders.