MiRNA-337 leads to podocyte injury in mice with diabetic nephropathy

S.-M. Zhao, T. Zhang, Q. Qiu, C. Xu, L.-J. Ma, J. Liu, Z. Wang, Y.-C. Li, J. Huang, M. Zhang

Department of Nephrology, Beijing Chao-Yang Hospital of Capital Medical University, Beijing, China. 1274834875@qq.com

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• Nephrology

OBJECTIVE: To elucidate the function of miRNA-337 in the pathogenesis of diabetic nephropathy (DN) and its underlying mechanism.

MATERIALS AND METHODS: Type 2 diabetes db/db mice were assigned into db/db group, vehicle group, and si-miR group, and age-matched db/m mice were in the db/m group. Differences in mouse serum glucose, body weight, serum creatinine, and albumin/creatinine ratio (ACR) among the four groups were compared at 6 weeks, 10 weeks, 14 weeks, 18 weeks, and 22 weeks of age. The expression level of miRNA-337 in mouse kidney tissues was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Correlation between miRNA-337 expression with ACR was analyzed. Through Western blot analysis, protein levels of interleukin 6 (IL-6), IL-18, podocin, nephrin, and desmin in mouse kidney tissues were detected.

RESULTS: With the increasing age, serum glucose, body weight, serum creatinine, and ACR in db/db mice gradually increased, which were remarkably higher than age-matched db/m mice. After treatment with miRNA-337 inhibitor in db/db mice, no remarkable changes in serum glucose and body weight were found, while serum creatinine and ACR decreased. Compared with db/m mice, miRNA-337 expression in kidney tissues of db/db mice upregulated, which was positively correlated with ACR. Expression levels of IL-6 and IL-18 in kidney tissues of db/db mice increased relative to db/m mice, but they were downregulated by miRNA-337 inhibitor treatment. Moreover, podocin and nephrin downregulated, while desmin upregulated in kidney tissues of db/db mice than db/m mice. By miRNA-337 inhibitor treatment in db/db mice, levels of podocin and nephrin increased, whereas desmin level decreased. We obtained similar results at their cellular level.

CONCLUSIONS: We showed that miRNA-337 expression increases in db/db mice with diabetic nephropathy, which leads to podocyte injury by upregulating levels of IL-6 and IL-18.

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