Diabetes, Metabolic Syndrome and Obesity (Feb 2020)

Silencing of KCNQ1OT1 Decreases Oxidative Stress and Pyroptosis of Renal Tubular Epithelial Cells

  • Zhu B,
  • Cheng X,
  • Jiang Y,
  • Cheng M,
  • Chen L,
  • Bao J,
  • Tang X

Journal volume & issue
Vol. Volume 13
pp. 365 – 375

Abstract

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Bei Zhu,1 Xingbo Cheng,2 Yilan Jiang,3 Ming Cheng,4 Luping Chen,3 Jiajun Bao,3 Xiaofeng Tang3 1Department of Endocrinology, The First Affiliated Hospital of Soochow University, Suzhou 215006, People’s Republic of China, Department of Endocrinology, Rugao People’s Hospital, Nantong 226500, People’s Republic of China; 2Department of Endocrinology, The First Affiliated Hospital of Soochow University, Suzhou 215006, People’s Republic of China; 3Department of Endocrinology, Rugao People’s Hospital, Nantong 226500, People’s Republic of China; 4School of Rail Transportation, Soochow University, Suzhou 215131, People’s Republic of ChinaCorrespondence: Xingbo ChengDepartment of Endocrinology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, People’s Republic of ChinaEmail [email protected] ChengSchool of Rail Transportation, Soochow University, 8 Ji Xue Road., Xiangcheng District, Suzhou 215131, People’s Republic of ChinaEmail [email protected]: Long noncoding RNAs (lncRNAs) can regulate the progression of DN. This research aimed to study the effect of lncRNA KCNQ1OT1 on the oxidative stress and pyroptosis of the renal tubular epithelial cells induced by high glucose (HG).Methods: RT-qPCR analysis detected the KCNQ1OT1 expression in serum with DN and HG-induced HK-2 cells, detect the expression of NLRP3, cleaved-caspase1, P-caspase1, IL-1β, p-IL-1β and GSDMD-N in HG-induced HK-2 cells, and confirm the transfection effects. The expression of NLRP3, cleaved-caspase1, P-caspase1, IL-1β, p-IL-1β and GSDMD-N in HG-induced HK-2 cells was also analyzed by Western blot analysis. ELISA assay detected the levels of TNF-α, IL-6 and MCP-1. The levels of ROS, MDA and SOD were determined by respective ELISA kits and ROS was also detected by the ROS assay kit (containing DCFH-DA).Results: We found that KCNQ1OT1 was increased in the plasma of patients with DN and HG-induced HK-2 cells and KCNQ1OT1 interference could decrease the inflammation, oxidative stress and pyroptosis of HG-induced HK-2 cells. In addition, KCNQ1OT1 directly targets miR-506-3p. MiR-506-3p was downregulated in the plasma of patients with DN and HG-induced HK-2 cells and KCNQ1OT1 interference promoted the expression of miR-506-3p. MiR-506-3p overexpression suppressed the inflammation, oxidative stress and pyroptosis of HG-induced HK-2 cells.Conclusion: This study demonstrated that downregulation of KCNQ1OT1 inhibited the inflammation, oxidative stress and pyroptosis of HG-induced HK-2 cells by up-regulating the expression of miR-506-3p, which provide new insights into the treatment of DN.Keywords: LncRNA KCNQ1OT1, oxidative stress, pyroptosis, diabetic nephropathy, renal tubular epithelial cells

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