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

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

• Hsu YH
• Li HH
• Sung JM
• Chen WY
• Hou YC
• Weng YH
• Lai WT
• Wu CH
• Chang MS

• KMID: 2375797
• DOI: http://doi.org/10.1038/emm.2016.169

Abstract

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
Apoptosis
Blood Glucose
Caspase 8
Diabetes Mellitus
Diabetic Nephropathies*
Enzyme-Linked Immunosorbent Assay
Glucose
Humans
Hydrogen Peroxide
In Vitro Techniques
Interleukin-10
Interleukins
Kidney
Kidney Failure, Chronic
Mice
Podocytes*
Rats
Vascular Endothelial Growth Factor A
Blood Glucose
Caspase 8
Glucose
Hydrogen Peroxide
Interleukin-10
Interleukins
Vascular Endothelial Growth Factor A