The purpose of this study was to explore the functional implication of microRNA-218 (miR-218) in diabetic nephropathy (DN) through high-glucose-stimulated renal proximal tubule impairment. Biological function experiments showed that miR-218 and inflammatory factors TNF-α and IL-1β were highly expressed in renal proximal tubule under high-glucose conditions. Inhibiting miR-218 alleviated renal tubular cell injury, which was represented by miR-218 inhibitor facilitating renal tubular cell vitality whilst reducing its apoptosis and levels of inflammation factors. In addition, we confirmed that miR-218 directly targeted GPRC5A and negatively regulated its expression. Co-transfection assay showed that overexpression of GPRC5A accentuated the mitigated action of miR-218 inhibitor on renal proximal tubule cell injury induced by high-glucose. Accordingly, these data indicated that downregulation of miR-218 can assuage high-glucose-resulted renal tubular cell damage, and its ameliorative effect was achieved by negative regulation of GPRC5A, which provides a novel direction for unearthing the pathogenesis and even further biological treatment of DN.

中文翻译：

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MiR-218的下调可通过靶向GPRC5A减轻高糖诱导的肾近端小管损伤。

这项研究的目的是通过高糖刺激的肾近端肾小管损伤，探讨microRNA-218（miR-218）在糖尿病肾病（DN）中的功能含义。生物学功能实验表明，在高糖条件下，miR-218和炎症因子TNF-α和IL-1β在肾近端小管中高表达。抑制miR-218可减轻肾小管细胞损伤，其表现为miR-218抑制剂可促进肾小管细胞活力，同时减少其凋亡和炎症因子水平。此外，我们证实miR-218直接靶向GPRC5A并对其表达负调控。共转染试验表明，GPRC5A的过表达增强了miR-218抑制剂对高糖诱导的肾小管细胞损伤的缓解作用。因此，