LncRNA MALAT1 promoted high glucose-induced pyroptosis of renal tubular epithelial cell by sponging miR-30c targeting for NLRP3.

Abstract

Diabetic nephropathy (DN), characterized by the chronic loss of kidney function during diabetes, is a long-term kidney disease that affects millions of populations. However, the etiology of DN remains unclear. DN cell model was established by treating HK-2 cells with high glucose (HG) in vitro. Expression of metastasis-associated lung adenocarcinoma transcript-1 (MALAT1), miR-30c, nucleotide binding and oligomerization domain-like receptor protein 3 (NLRP3), caspase-1, IL-1β, and IL-18 in treated HK-2 cells were tested by quantitative polymerase chain reaction. HK-2 cell pyroptosis was assessed using flow cytometry analysis. Lactate dehydrogenase (LDH) activity was examined with a LDH assay kit. Correlation among MALAT1, miR-30c, and NLRP3 was examined via dual-luciferase reporter assay. Here, we revealed that MALAT1 was upregulated, but miR-30c was downregulated in HG-treated HK-2 cells, leading to upregulation of NLRP3 expression and cell pyroptosis. Knockdown of MALAT1 or overexpression of miR-30c protected HK-2 cells from HG-induced pyroptosis. Meanwhile, we found that MALAT1 promoted NLRP3 expression by sponging miR-30c through dual-luciferase reporter assay. Moreover, the co-transfection of sh-MALAT1 and miR-30c inhibitor could reverse the protective effects of the sh-MALAT1 on the HG-induced pyroptosis. These results confirmed that MALAT1 regulated HK-2 cell pyroptosis by inhibiting miR-30c targeting for NLRP3, contributing to a better understanding of DN pathogenesis and help to find out the effective treatment for DN.