Tetratricopeptide repeat domain 36 deficiency mitigates renal tubular injury by inhibiting TGF-b1-induced epithelial-mesenchymal transition in a mouse model of chronic kidney disease

作者全名："Yan, Xin; Peng, Rui; Ni, Yilu; Chen, Lei; He, Qingling; Li, Qianyin; Zhou, Qin"

作者地址："[Yan, Xin; Peng, Rui; Ni, Yilu; Chen, Lei; He, Qingling; Li, Qianyin; Zhou, Qin] Chongqing Med Univ, Sch Lab Med, Minist Educ Key Lab Clin Diagnost, Chongqing 400016, Peoples R China"

通信作者："Li, QY; Zhou, Q (通讯作者)，Chongqing Med Univ, Sch Lab Med, Minist Educ Key Lab Clin Diagnost, Chongqing 400016, Peoples R China."

来源：GENES & DISEASES

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000870272400006

JCR分区：Q1

影响因子：6.8

年份：2022

卷号：9

期号：6

开始页：1716

结束页：1726

文献类型：Article

关键词：CCAAT enhancer binding protein beta; Chronic kidney disease; Epithelial-mesenchymal transition; Renal fibrosis; SMAD family bember 3; Tetratricopeptide repeat domain 36

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 epithelial-mesenchymal transition (EMT), which in turn aggravates tubular injury and kidney fibrosis. In this study, we firstly revealed that the reduction of TTC36 is asso-ciated 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-I31-induced HK2 cells. Moreover, TTC36 elevated the protein expression of CEBPB, which was involved in the regulation of TGF-I3/SMAD3 signaling, and augmented SMAD3 signaling and downstream genetic response were reduced by CEBPB silencing. Collectively, our results uncovered that TTC36 deficiency plays a protec-tive role in tubular injury and renal fibrosis triggered by UUO; further, TTC36 overexpression exacerbated TGF-I3/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. Copyright (c) 2021, Chongqing Medical University. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/ by-nc-nd/4.0/)."

基金机构：National Natural Science Foundation of China; Scien-tific and Technological Research Program of Chongqing Municipal Education Commission; Chongqing Science and Technology Commission; [81873932]; [81802549]; [KJQN202000438]; [cstc2019jscx-dxwtBX0032]

基金资助正文："Funding This work was supported by the National Natural Science Foundation of China (No. 81873932, 81802549) , the Scien-tific and Technological Research Program of Chongqing Municipal Education Commission (No. KJQN202000438) and Chongqing Science and Technology Commission (No. cstc2019jscx-dxwtBX0032) ."