Interleukin-20 targets podocytes and is upregulated in experimental murine diabetic nephropathy

Exp Mol Med. 2017 Mar 31;49(3):e310. doi: 10.1038/emm.2016.169.


Interleukin (IL)-20, a proinflammatory cytokine of the IL-10 family, is involved in acute and chronic renal failure. The aim of this study was to elucidate the role of IL-20 during diabetic nephropathy development. We found that IL-20 and its receptor IL-20R1 were upregulated in the kidneys of mice and rats with STZ-induced diabetes. In vitro, IL-20 induced MMP-9, MCP-1, TGF-β1 and VEGF expression in podocytes. IL-20 was upregulated by hydrogen peroxide, high-dose glucose and TGF-β1. In addition, IL-20 induced apoptosis in podocytes by activating caspase-8. In STZ-induced early diabetic nephropathy, IL-20R1-deficient mice had lower blood glucose and serum BUN levels and a smaller glomerular area than did wild-type controls. Anti-IL-20 monoclonal antibody (7E) treatment reduced blood glucose and the glomerular area and improved renal functions in mice in the early stage of STZ-induced diabetic nephropathy. ELISA showed that the serum IL-20 level was higher in patients with diabetes mellitus than in healthy controls. The findings of this study suggest that IL-20 induces cell apoptosis of podocytes and plays a role in the pathogenesis of early diabetic nephropathy.

MeSH terms

  • Animals
  • Antibodies, Neutralizing / pharmacology
  • Apoptosis
  • Blood Glucose / metabolism
  • Case-Control Studies
  • Cell Line
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Diabetic Nephropathies / metabolism*
  • Humans
  • Interleukins / antagonists & inhibitors
  • Interleukins / genetics
  • Interleukins / metabolism*
  • Kidney / metabolism
  • Male
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Podocytes / metabolism*
  • Rats
  • Rats, Wistar
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin / metabolism
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism
  • Up-Regulation*
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism


  • Antibodies, Neutralizing
  • Blood Glucose
  • Chemokine CCL2
  • Interleukins
  • Receptors, Interleukin
  • Transforming Growth Factor beta1
  • Vascular Endothelial Growth Factor A
  • interleukin-20 receptor
  • Matrix Metalloproteinase 9
  • interleukin 20