MiR-200c-3p regulates pyroptosis by targeting SLC30A7 in diabetic retinopathy

上睑下垂 基因敲除 流式细胞术 细胞凋亡 小RNA 糖尿病性视网膜病变 下调和上调 化学 细胞生物学 程序性细胞死亡 癌症研究 生物 糖尿病 免疫学 生物化学 基因 内分泌学
作者
Weina Li,Sheng Yang,Guangsheng Chen,Shiping He
出处
期刊:Human & Experimental Toxicology [SAGE Publishing]
卷期号:41: 9603271221099589-9603271221099589 被引量:22
标识
DOI:10.1177/09603271221099589
摘要

Clinical relevance: MicroRNAs (miRNAs) have been reported to be involved in the progression of various diseases. Studying the regulatory mechanisms of miRNAs can help clinical treatment. Background: Diabetic retinopathy (DR) is one of the complications of diabetes. The objective of this study was to elucidate the underlying molecular mechanisms by which miR-200c-3p regulates the pyroptosis of DR cell. Methods: Human retinal microvascular endothelial cells (HRMECs) and high glucose (HG) cultures established DR cell model in vitro. RT-qPCR is used to detect the expression level of miRNAs. CCK-8 assays and flow cytometry are used to detect apoptosis of HRMECs cell. Western blotting is used to detect cleaved caspase-3, cleaved caspase-1, and N-GSDMD proteins levels in HRMECs. The ELISA assay is used to detect the expression of IL-1β and IL-18. Predict and validate potential binding sites between miR-200c-3p and SLC30A7 by dual luciferase reporter gene analysis. Results: The results showed that HG caused damage to HRMECs through the pyroptosis pathway rather than the apoptosis pathway. MiR-200c-3p is highly expressed in HG induced-HRMECs, and knockdown of miR-200c-3p mitigates HG-induced HRMECs pyroptosis. MiR-200c-3p negatively targets SLC30A7 in HRMECs, and miR-200c-3p regulates pyroptosis of HG-induced HRMECs by targeting SLC30A7. Conclusion: The results suggest that miR-200c-3p might be a promising interference target for DR prevention and treatment. The results of current study may provide new insights into development of therapeutic strategies for DR.
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