High expression of LncRNA-MALAT1 in renal tubular cells induced by high glucose and its promotion role on pyroptosis by regulating miR-206

Background: Diabetic nephropathy (DN) is the main reason for renal failure in terminal stage. Studies have shown that long-chain non-coding RNA (LncRNA) improves DN by regulating microRNA (miR). The study intended to investigate the role of MALAT1/miR-206 on high glucose (HG)-induced inflammation, oxidative stress and cell death of renal tubular epithelial cells (RTECs). Methods: HG-intervened HK-2 cells to establish DN cell model. Transfection effect was confirmed by qRT-PCR and MALAT1, NLRP3, Caspase-1, IL-1 beta, GSMDD-N and miR-206 were tested. Western blot was performed to test the proteins in NLRP3, Caspase-1, IL-1 beta and GSMDD-N, and to observe the pyroptosis. Elisa kit was applied to detect TNF-alpha, IL-6 and MCP-1. Results: Double luciferase report experiment and RNA immunoprecipitation (RIP) confirmed that MALAT1 could bind to miR-206. HG induced MALAT1 in HK-2 cells increased. Knocking down MALAT1 could reduce TNF-alpha, IL-6 and MCP-1. In HG-intervened HK-2 cells, the over-expressed miR-206 transfected into the cells was consistent with the changes of inflammatory factors and cytokines after knock-down MALAT1. Conclusion: Up-regulation MALAT1 could reverse the inhibition of miR-206 on pyroptosis and inflammatory response. MALAT1 can improve HG-induced HK-2 pyroptosis by targeting miR-206, which is expected to be a latent target to treat DN in clinic. (C) 2021 The Authors. Published by Elsevier B.V. on behalf of King Saud University.

Automated summary

This study investigated the role of MALAT1/miR-206 in high glucose-induced inflammation, oxidative stress, and cell death of renal tubular epithelial cells. The results demonstrated that up-regulation of MALAT1 can reverse the inhibition of miR-206 on pyroptosis and inflammatory response, providing a potential target for treating DN in the clinic.