IRE1α dissociates with BiP and inhibits ER stressmediated apoptosis in cartilage development
作者单位：Department of Cell Biology and GeneticsCore Facility of Development BiologyChongqing Medical University Laboratory of Stem Cells and Tissue EngineeringChongqing Medical University
会议名称：《中国遗传学会第九次全国会员代表大会暨学术研讨会》
会议日期：2013年
学科分类：1001[医学-基础医学(可授医学、理学学位)] 100104[医学-病理学与病理生理学] 10[医学]
基 金：supported by National Science Foundation of China Grant 81171697 Natural Science Foundation Project of CQ CSTC Grant 2011jjA10047 University Excellent Talent Support Project of Chong-Qing Education Committee Grant 2011-65
关 键 词：Endoplasmic reticulum stress Apoptosis UPR IRE1α BiP cartilage development
摘 要：Bone morphogenetic protein 2 is known to activate unfolded protein response signaling molecules,including XBP1S,BiP and IREIα.Endoplasmic Reticulum stress is induced in chondrogenesis and activates IRE lαsignal pathway,which is associated with ER stress-mediated ***,the influence on IRElαt and BiP in BMP2-induced chondrocyte differentiation have not yet been elucidated,the molecular mechanism remains unexplored. In this study,we demonstrate that IRE1αinteracts with BiP in unstressed cells and dissociates from BiP in the course of cartilage *** of ER stress-responsive proteins (XBPIS,IRE1α,BiP) was also observed in differentiating ***αinhibition ER stress-mediated apoptosis lies in the process of chondrocyte ***, knockdown of IRE1αexpression by way of the RNAi approach accelerates ER stress-mediated apoptosis in ehondrocyte differentiation induced by BMP2,as revealed by enhanced expression of cleaved caspase3,CHOP and p-JNK1;and this IRE1αinhibition effect on ER stress-mediated apoptosis is required for BiP in chondrogenesis. Collectively,the ER stress sensors were activated during apoptosis in cartilage development, suggesting that selective activation of ER stress signaling was sufficient for induction of apoptosis These findings reveal a novel critical role of IRElαin ER stress-mediated apoptosis and the molecular mechanisms *** results suggest that activation of p-JNKl,caspase3 and CHOP were detected in developing chondrocytes and that specific ER stress signaling leads to naturally occurring apoptosis during cartilage development.