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

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.

• Authors: Yu-Hsiang Hsu, Hsing-Hui Li, Junne-Ming Sung, Wei-Yu Chen, Ya-Chin Hou, Yun-Han Weng, Wei-Ting Lai, Chih-Hsing Wu, Ming-Shi Chang
• Journal: Experimental & molecular medicine (Exp Mol Med) Vol. 49 Issue 3 Pg. e310 (03 31 2017) ISSN: 2092-6413 [Electronic] United States
• PMID: 28360429 (Publication Type: Journal Article)

Chemical References

• 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

Topics

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