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eISSN: 1643-3750

β-Arrestin 1/2 Aggravates Podocyte Apoptosis of Diabetic Nephropathy via Wnt/β-Catenin Pathway

Yao Wang, Han Li, Shu-Ping Song

Department of Endocrinology, Tianjin Hospital, Tianjin, China (mainland)

Med Sci Monit 2018; 24: LBR1724-1732

DOI: 10.12659/MSM.905642

Available online: 2018-03-24

Published: 2018-03-24


#905642

BACKGROUND: β-arrestins have been shown to play a critical role in the progression of diabetic nephropathy. Nevertheless, the potential mechanism of β-arrestins on the regulation of podocyte apoptosis has rarely been discussed. This study aimed to elucidate the regulation of β-arrestin 1/2 on podocyte apoptosis through the Wnt/b-catenin pathway.
MATERIAL AND METHODS: This study structured β-arrestin 1/2 down-regulated and up-regulated expression by plasmid transfection. The protein levels were detected with Western blotting, and mRNA expression was detected with RT-qPCR. The apoptotic cells were measured by flow cytometry.
RESULTS: β-arrestin 1/2 expression levels of podocytes were up-regulated in high-glucose-induced podocytes. β-arrestin 1/2 overexpression inhibited the expression of nephrin and podocin protein. Up-regulated β-arrestin 1/2 promoted podocyte apoptosis and p53 pathway by increasing Bax, cleaved caspase-3, and p-p53 levels in high-glucose-induced podocytes. Flow cytometry showed that the apoptotic cells were markedly higher in the b-arrestin 1/2 up-regulated group compared with the scramble group. Expression of β-catenin was increased in the β-arrestin 1/2 up-regulated group, which indicated that the Wnt/b-catenin pathway was activated. Wnt/b-catenin pathway inhibitor (Dkk1) distinctly suppressed the apoptosis induced by β-arrestin 1/2 overexpression and high glucose.
CONCLUSIONS: These results provide a molecular pathomechanism of β-arrestin 1/2 and Wnt/β-catenin pathway on podocyte apoptosis and provide new ideas for the treatment of diabetic nephropathy, which paves the way for the future study of diabetic nephropathy and podocytes.

Keywords: Diabetic Nephropathies, Podocytes, Wnt Signaling Pathway



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