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. 2020 Apr;235(4):3362-3371.
doi: 10.1002/jcp.29224. Epub 2019 Sep 24.

miR-218 regulates diabetic nephropathy via _targeting IKK-β and modulating NK-κB-mediated inflammation

Mo Li  1 , Qiushi Guo  2 , Hanqing Cai  1 , Haiyang Wang  1 , Zhiming Ma  3 , Xuan Zhang  4
Affiliations

miR-218 regulates diabetic nephropathy via _targeting IKK-β and modulating NK-κB-mediated inflammation

Mo Li et al. J Cell Physiol. 2020 Apr.

Abstract

Diabetic nephropathy (DN) is a common clinically relevant complication of diabetes that is associated with damage to the capillaries, yet the etiology of this condition remains unclear. Nuclear factor-kappa B (NF-κB) activation is known to be associated with DN-related inflammation and disease progression. Recent work indicated that microRNAs are diagnostic biomarkers of DN progression associated with inflammation in the progression of DN. miR-218 is known to play key regulatory roles in certain cancers in humans, while its influence on DN pathology remains uncertain. The present study, therefore, sought to assess how miR-218 influences the progression of disease in both a rat streptozotocin-induced model of DN and as well as an in vitro model system in which mouse podocytes were stimulated with high glucose levels. We found miR-218 to be markedly downregulated in both model systems relative to appropriate controls, and this downregulation was associated with IKK-β upregulation. In DN rat model, overexpressing miR-218 was sufficient to reduce renal injury. We further determined that podocyte proliferation was markedly impaired by glucose treatment, leading to the apoptotic death of these cells, and miR-218 mimics were able to reduce these phenotypes. Overexpressing miR-218 also significantly dampened inflammatory responses in this model system, as evidenced by reduced tumor necrosis factor-α, interleukin-6 (IL-6), IL-1β, and MCP-1 levels. We then confirmed that miR-218 _targeting the messenger RNA encoding IKK-β using a dual-luciferase reporter assay. Together, our results provide clear evidence that miR-218 regulate NF-κB-mediated inflammation, which is central to DN progression.

Keywords: IKK-β; NF-κB; diabetic nephropathy; inflammatory; miR-218.

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