Tetratricopeptide repeat domain 36 deficiency mitigates renal tubular injury by inhibiting TGF-β1-induced epithelialemesenchymal transition in a mouse model of chronic kidney disease  

作　　者：Xin Yan Rui Peng Yilu Ni Lei Chen Qingling He Qianyin Li Qin Zhou 

机构地区：[1]The Ministry of Education Key Laboratory of Clinical Diagnostics,School of Laboratory Medicine,Chongqing Medical University,Chongqing 400016,PR China

出　　处：《Genes & Diseases》2022年第6期1716-1726,共11页基因与疾病（英文）

基　　金：This work was supported by the National Natural Science Foundation of China(No.81873932,81802549);the Scientific and Technological Research Program of Chongqing Municipal Education Commission(No.KJQN202000438);Chongqing Science and Technology Commission(No.cstc2019jscx-dxwtBX0032).

摘　　要：The damage of proximal tubular epithelial cells(PTECs)is considered a central event in the pathogenesis of chronic kidney disease(CKD)and deregulated repair processes of PTECs result in epithelialemesenchymal transition(EMT),which in turn aggravates tubular injury and kidney fibrosis.In this study,we firstly revealed that the reduction of TTC36 is associated with unilateral ureteral obstruction(UUO)-induced CKD;besides,ablation of TTC36 attenuated tubular injury and subsequent EMT in UUO-treated mice kidneys.Consistently,TTC36 overexpression promoted EMT in TGF-β1-induced HK2 cells.Moreover,TTC36 elevated the protein expression of CEBPB,which was involved in the regulation of TGF-β/SMAD3 signaling,and augmented SMAD3 signaling and downstream genetic response were reduced by CEBPB silencing.Collectively,our results uncovered that TTC36 deficiency plays a protective role in tubular injury and renal fibrosis triggered by UUO;further,TTC36 overexpression exacerbated TGF-β/SMAD3 signaling via elevating the stability of SMAD3 and CEBPB,suggesting that TTC36 inhibition may be a potential strategy in the therapy of obstructive nephropathy.

关 键 词：CCAAT enhancer binding protein beta Chronic kidney disease Epithelialmesenchymal transition Renal fibrosis SMADfamilybember 3 Tetratricopeptide repeat domain 36 

分 类 号：R692[医药卫生—泌尿科学]