MicroRNA-544 attenuates diabetic renal injury via suppressing glomerulosclerosis and inflammation by targeting FASN

Gene. 2020 Jan 10:723:143986. doi: 10.1016/j.gene.2019.143986. Epub 2019 Jul 16.

Abstract

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Accumulating evidence shows that microRNAs play important roles in diabetic kidney. However, the potential role of MicroRNA-544 (miR-544) in DN remains unclear. In this study, we explored the role of miR-544 on inflammation and fibrosis in diabetic kidney using db/db mice. Renal expression of miR-544 was decreased in mice, companied by increased the expression of FASN. The dual luciferase assay confirmed FASN as a direct target of miR-544. Over-expression of miR-544 significantly ameliorated renal injury, mesangial matrix and renal fibrosis. In addition, over-expression of miR-544 significantly attenuated inflammatory cells infiltration and IL-1, IL-6, TNF- and iNOS production in DN. Furthermore, miR-544 over-expression inhibited the activation of NF-kB signal pathway in DN. In conclusion, our finding demonstrated that miR-544 attenuates diabetic renal injury via suppressing glomerulosclerosis and inflammation by targeting FASN, suggesting that miR-544 might have therapeutic potential for the treatment of DN.

Keywords: Diabetic nephropathy; FASN; Fibrosis; Inflammation; miR-544.

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Cytokines / metabolism*
  • Diabetic Nephropathies / genetics*
  • Diabetic Nephropathies / immunology
  • Disease Models, Animal
  • Down-Regulation
  • Fatty Acid Synthase, Type I / genetics*
  • HEK293 Cells
  • Humans
  • Interleukin-1 / metabolism
  • Interleukin-6 / metabolism
  • Mice
  • MicroRNAs / genetics*
  • NF-kappa B / metabolism
  • Nitric Oxide Synthase Type II / metabolism*
  • Receptors, Leptin / genetics
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation

Substances

  • 3' Untranslated Regions
  • Cytokines
  • Interleukin-1
  • Interleukin-6
  • MIRN544 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • Receptors, Leptin
  • Tnf protein, mouse
  • Tumor Necrosis Factor-alpha
  • interleukin-6, mouse
  • leptin receptor, mouse
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • FASN protein, human
  • Fatty Acid Synthase, Type I