MiR‐874 alleviates renal injury and inflammatory response in diabetic nephropathy through targeting toll‐like receptor‐4

Diabetic nephropathy (DN) is a kind of diabetic complication with capillary damage, and its pathogenesis remains obscure. Recently, microRNAs have been identified as diagnostic biomarkers in various diseases including DN. Toll‐like receptor 4 (TLR4) contributes to inflammation, and it has been implicated in diabetes pathophysiology. This study was designed to investigate the role of miR‐874 and TLR4 in a streptozotocin (STZ)‐induced DN rat model and glucose‐induced mouse podocyte model. In the current study, we reported that miR‐874 was markedly downregulated in DN rats and glucose‐induced mouse podocytes compared with the corresponding control groups with the activation of TLR4. In addition, we observed that overexpression of miR‐874 was able to alleviate renal injury in DN rats. The cell counting kit (CCK‐8) assay and 5‐Ethynyl‐2′‐deoxyuridine (EdU) assay demonstrated that glucose simulation significantly inhibited podocyte proliferation and induced cell apoptosis, which can be reversed by miR‐874 mimics significantly. Notably, miR‐874 overexpression dramatically attenuated the inflammatory response, indicated by the decreased levels of interleukin‐6, L‐1β, and tumor necrosis factor α (TNF‐α). Finally, the binding correlation between miR‐874 and TLR4 was confirmed by carrying out dual‐luciferase reporter assay in our study. It was found that overexpression of miR‐874 depressed TLR4 levels in podocytes. These findings implied for the first time that the overexpression of miR‐874 repressed glucose‐triggered podocyte injury through targeting TLR4 and suggested that miR‐874/TLR4 axis might represent a pathological mechanism of DN. We found that expression of miR‐874 was decreased, whereas toll‐like receptor 4 (TLR4) was increased in diabetic nephropathy (DN) rats, and overexpression of miR‐874 ameliorated DN through alleviating renal injury and inflammatory response in streptozotocin‐induced DN rat model and high‐glucose–induced podocytes. It was proved that miR‐874 was able to inhibit DN development through targeting TLR4; however, the molecular correlation between miR‐874 and TLR4 of DN still need more investigation. In conclusion, it is the first time to uncover that miR‐874 might serve as a biomarker and therapeutic target in DN.