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

Background: beta-arrestins have been shown to play a critical role in the progression of diabetic nephropathy. Nevertheless, the potential mechanism of beta-arrestins on the regulation of podocyte apoptosis has rarely been discussed. This study aimed to elucidate the regulation of beta-arrestin 1/2 on podocyte apoptosis through the Wnt/beta-catenin pathway. Material/Methods: This study structured beta-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: beta-arrestin 1/2 expression levels of podocytes were up-regulated in high-glucose-induced podocytes. beta-arrestin 1/2 overexpression inhibited the expression of nephrin and podocin protein. Up-regulated beta-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 beta-arrestin 1/2 up-regulated group compared with the scramble group. Expression of beta -catenin was increased in the b-arrestin 1/2 up-regulated group, which indicated that the Wnt/beta-catenin pathway was activated. Wnt/beta-catenin pathway inhibitor (Dkk1) distinctly suppressed the apoptosis induced by beta-arrestin 1/2 overexpression and high glucose. Conclusions: These results provide a molecular pathomechanism of beta-arrestin 1/2 and Wnt/beta-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.