Objective: This report was designed to assess the functional role of miR-218/dachshund family transcription factor 1 (DACH1) in diabetic kidney disease (DKD) and investigate its possible molecular mechanism.Materials and Methods: From the GEO database, we downloaded different datasets for analyzing the expression of miR-218 and DACH1 in DKD. TargetScan was adopted to predict the binding sites between miR-218 and DACH1, which was further verified by dual-luciferase reporter assays. The renal proximal tubule cells (HK-2) treated with high glucose (HG) were used as an in vitro model. QRT-PCR and western blot were used to determine the expression of DACH1 and other relative factors. Cell counting kit-8 and flow cytometer were applied to detect cell viability and apoptosis. The levels of inflammatory cytokines were determined by an ELISA assay.Results: A prominent raise of miR-218 was observed in DKD through bioinformatics analysis, which was further confirmed in the HG-induced model. DACH1 is a target of miR-218. miR-218 reduced cell viability and induced apoptosis by negatively regulating DACH1. Moreover, upregulating miR-218 in HG models increased the concentrations of pro-inflammatory cytokines TNF-α and IL-1β, reduced the level of anti-inflammatory cytokine IL-10, and promoted the epithelial-mesenchymal transition (EMT) process, which is possibly achieved by targeting DACH1. While downregulating miR-218 showed the opposite results.Conclusion: These data demonstrated that, under an in vitro HG environment, miR-218 suppressed the HK-2 cells proliferation, promoted apoptosis, caused an inflammatory response, and facilitated the EMT process largely by targeting DACH1, providing an insight into the therapeutic intervention of DKD.

中文翻译：

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DACH1是miR-218的新靶标，参与高糖治疗的肾小管细胞的细胞活力，凋亡，炎症反应和上皮-间质转化过程的调节。

目的：本报告旨在评估miR-218 /腊肠犬转录因子1（DACH1）在糖尿病肾病（DKD）中的功能，并探讨其可能的分子机制。材料与方法：从GEO数据库下载了不同的分析miR-218和DACH1在DKD中表达的数据集。采用TargetScan预测miR-218与DACH1之间的结合位点，这已通过双荧光素酶报告基因检测进一步证实。高糖（HG）处理的肾近端肾小管细胞（HK-2）被用作体外模型。采用QRT-PCR和western blot检测DACH1的表达及其他相关因素。应用细胞计数试剂盒8和流式细胞仪检测细胞活力和凋亡。通过ELISA法测定炎症细胞因子的水平。通过生物信息学分析在DKD中观察到miR-218的显着升高，这在HG诱导的模型中得到了进一步证实。DACH1是miR-218的靶标。miR-218通过负调节DACH1降低细胞活力并诱导凋亡。此外，在HG模型中上调miR-218可增加促炎细胞因子TNF-α和IL-1β的浓度，降低抗炎细胞因子IL-10的水平，并促进上皮-间质转化（EMT）过程，可以通过针对DACH1来实现。结论：这些数据表明，在体外HG环境下，miR-218抑制HK-2细胞增殖，促进细胞凋亡，引起炎症反应，并在很大程度上促进了EMT过程。定位到DACH1，