期刊
GENES & DISEASES
卷 9, 期 6, 页码 1716-1726出版社
ELSEVIER
DOI: 10.1016/j.gendis.2021.04.005
关键词
CCAAT enhancer binding protein beta; Chronic kidney disease; Epithelial-mesenchymal transition; Renal fibrosis; SMAD family bember 3; Tetratricopeptide repeat domain 36
资金
- 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]
This study revealed the association between TTC36 reduction and CKD induced by unilateral ureteral obstruction (UUO), and showed that ablation of TTC36 attenuated tubular injury and subsequent EMT. TTC36 overexpression promoted EMT in TGF-I31-induced HK2 cells. Moreover, TTC36 elevated the protein expression of CEBPB, which regulated TGF-I3/SMAD3 signaling.
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/).
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