Diabetes, Metabolic Syndrome and Obesity (Apr 2021)
Atorvastatin Regulates MALAT1/miR-200c/NRF2 Activity to Protect Against Podocyte Pyroptosis Induced by High Glucose
Abstract
Yi Zuo,1 Li Chen,2 Xiaoyun He,3 Zhen Ye,2 Ling Li,1 Zhanhong Liu,1 Suxian Zhou1 1Department of Endocrinology, Affiliated Hospital of Guilin Medical University, Guilin, 541001, People’s Republic of China; 2Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin, Guangxi, 541004, People’s Republic of China; 3Department of Endocrinology, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of ChinaCorrespondence: Suxian ZhouDepartment of Endocrinology, Affiliated Hospital of Guilin Medical University, 15 Lequn Road, Guilin, Guangxi, 541001, People’s Republic of ChinaEmail [email protected]: Diabetic nephropathy (DN) is one of the main complications of diabetes mellitus (DM), which leads to the long-term loss of kidney functions. Long noncoding RNAs (LncRNAs) can alleviate DN by interacting with microRNAs (miRNAs). In this work, we aimed to explore the effects of the MALAT1/miR-200c/NRF2 regulatory axis on the pyroptosis and oxidative stress (Oxidative stress, OS) of renal podocytes in high glucose (HG) environment and whether the lipid-lowering drug atorvastatin (AT) can relieve renal OS through this approach.Methods: MPC-5, a mouse podocyte cell line, was induced by HG as a cell model. The protein expressions of caspase-1, GSDMD, NLRP3, NRF2, etc. were detected by Western blotting and immunofluorescence, and the mRNA level of caspase-1, GSDMD, NLRP3, NRF2, MALAT1, miR-200c was tested by qRT-PCR. The cell pyroptosis of podocytes treated with AT was verified by CCK-8 or flow cytometry. The levels of Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) were measured by spectrophotometer, respectively.Results: The caspase-1 was upregulated in time-dependent manner and got the peak at 48 h and 30 mmol/L respectively in MPC-5 cells treated with HG. Further, the expression of GSDMD, MALAT1 and miR-200c were increased, while the level of NRF2, HO-1, OS-related indicators, were decreased simultaneously. Knockdown the MALAT1 protected MPC-5 cells from pyroptosis and OS induced by HG. However, overexpressing miR-200c in control-group cells increased pyroptosis and upregulated the OS level with HG culture medium. Further, atorvastatin protected MPC-5 cells from cell pyroptosis and downregulated the level of renal OS via attenuating the expression of MALAT1 and miR-200c.Conclusion: Atorvastatin protects podocyte cells via MALAT1/miR-200c/NRF2 signal pathway from pyroptosis and OS induced by HG.Keywords: atorvastatin, MALAT1, miR-200c, NRF2, podocytes, pyroptosis
