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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.

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


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.


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