Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan 430068, China.
Biochim Biophys Acta Gen Subj. 2019 Jul;1863(7):1210-1216. doi: 10.1016/j.bbagen.2019.04.016. Epub 2019 Apr 24.
Chronic exposure to cyclosporine causes nephrotoxicity and organ damage. Here we show that cyclosporine nephrotoxicity in vivo is associated with the activation of the unfolded protein response (UPR) pathway to initiate tissue fibrosis. We demonstrate that cyclosporine therapy activated the IRE1α branch of the unfolded protein response (UPR) and stimulated the TGFβ1 signaling pathway in the kidneys of male mice. Co-administration of the proteostasis promoter tauroursodeoxycholic acid (TUDCA) with cyclosporine inhibited the UPR pathway in the kidneys of treated male mice as well as decreased the development of renal fibrogenesis.
慢性暴露于环孢素会导致肾毒性和器官损伤。在这里，我们表明体内环孢素肾毒性与未折叠蛋白反应 (UPR) 途径的激活有关，从而引发组织纤维化。我们证明环孢素治疗激活了未折叠蛋白反应 (UPR) 的 IRE1α 分支，并刺激了雄性小鼠肾脏中的 TGFβ1 信号通路。与环孢素联合使用蛋白稳态促进剂牛磺熊脱氧胆酸 (TUDCA) 可抑制治疗雄性小鼠肾脏中的 UPR 途径，并减少肾纤维化的发展。
