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Front Biosci (Landmark Ed). 2020 Jan 1;25:593-605.

TMEM45A is involved in renal fibrosis in rats by regulating Jagged1/Notch pathway.

Author information

1
Department of Traditional Chinese Medicine, Shanghai East Hospital, Tongji University School of Medicine, NO.150, Jimo Road, Pudong District, Shanghai 200120, China.
2
Provincial Clinical Medical College, Fujian Medical University, NO. 88, Jiaotong Road, Fuzhou 350001, China, dffjsl112@126.com.

Abstract

Fibrosis, or the excess deposition of fibrous tissue, is a critical feature of chronic kidney disease. Here, using renal fibrotic rat as a model, which was established via 5/6 nephrectomy (Nx), the role of TMEM45A transmembrane protein in renal fibrosis was investigated. The results indicated that 5/6 Nx gradually led to histopathological abnormalities and loss of kidney function in rats, which correlated with upregulation of TMEM45A and Notch1. Interestingly, in NRK-49F renal cells, overexpression of TMEM45A resulted in up-regulation of extracellular matrix (ECM) components as well as induction of Notch-1 and Jagged-1. These effects were weakened by DAPT, an inhibitor of the Notch pathway, suggesting an important role of Notch signaling in mediating the functions of TMEM45A in NRK-49F cells Moreover, TMEM45A knockdown by TMEM45A siRNA in NRK-49F cells diminished TGF-b1-induced upregulation of ECM components, inflammatory cytokines, Notch-1 and Jagged-1. Correspondingly, TGF-beta 1 exhibited pro-fibrogenic like effect in NRK-49F cells and induced TMEM45A and Jagged1/Notch expression. Collectively, these results demonstrate that TMEM45A plays an important role in renal fibrosis by regulating ECM components and Jagged1/Notch pathway.

PMID:
31585906

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