Silencing long noncoding RNA-CES1P1 suppresses glomerular endothelial cell inflammation in diabetic nephropathy

Int Immunopharmacol. 2022 Sep:110:108820. doi: 10.1016/j.intimp.2022.108820. Epub 2022 Jul 11.

Abstract

Diabetic nephropathy (DN) has become the main cause of end-stage renal disease worldwide. Inflammation is associated with the occurrence and development of DN, and long noncoding RNAs (lncRNAs) are involved in the regulation of inflammatory processes. This study aims to determine the role and mechanism of lncRNA-CES1P1 in DN.C57BL/6 mice and human umbilical vein endothelial cells (HUVECs) were used for this experimental study. In vivo experimental intraperitoneal injection of streptozotocin (STZ) to construct a diabetes mellitus (DM) model in C57BL/6 mice caused increased expression of lncRNA-CES1P1, decreased expression of miR-214-3p in kidney tissue, and produced renal inflammation and proteinuria. Exogenous knockdown of lncRNA-CES1P1 expression decreased renal inflammatory infiltration. In vitro experiments using high glucose (HG) stimulation of HUVECs cell revealed increased expression of lncRNA-CES1P1, decreased expression of miR-214-3p, and increased expression of the inflammatory factors IL-17, IκB, NF-κB, and IL-6. Luciferase reporter assays showed direct targets of miR-214-3p interaction with lncRNA-CES1P1 and IL-17. These results suggest that hyperglycemia represses miR-214-3p by inducing lncRNA-CES1P1, which promotes the expression of the inflammatory factors IL-17, IκB, NF-κB and IL-6 ultimately leading to the development of DN. Interfering with lncRNA-CES1P1 can reduce hyperglycemia-induced DN.

Keywords: Diabetic nephropathy; IL-17; Inflammation; lncRNA-CES1P1; miR-214-3p.

MeSH terms

  • Animals
  • Diabetes Mellitus*
  • Diabetic Nephropathies* / genetics
  • Diabetic Nephropathies* / metabolism
  • Endothelial Cells / metabolism
  • Humans
  • Hyperglycemia* / genetics
  • Inflammation / genetics
  • Interleukin-17
  • Interleukin-6
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • NF-kappa B
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism

Substances

  • Interleukin-17
  • Interleukin-6
  • MIRN214 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • RNA, Long Noncoding