title: 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.affiliation: Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Research Center of Clinical Medicine, National Cheng Kung University Hospital, Tainan, Taiwan.|Research Center of New Antibody Drug, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yu-Hsiang
authors.initials: YH
authors.lastname: Hsu
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Hsing-Hui
authors.initials: HH
authors.lastname: Li
authors.affiliation: Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan.
authors.forename: Junne-Ming
authors.initials: JM
authors.lastname: Sung
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Wei-Yu
authors.initials: WY
authors.lastname: Chen
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Ya-Chin
authors.initials: YC
authors.lastname: Hou
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yun-Han
authors.initials: YH
authors.lastname: Weng
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Lai
authors.affiliation: Department of Family Medicine, National Cheng Kung University Hospital, Tainan, Taiwan.
authors.forename: Chih-Hsing
authors.initials: CH
authors.lastname: Wu
authors.affiliation: Research Center of New Antibody Drug, National Cheng Kung University, Tainan, Taiwan.|Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Ming-Shi
authors.initials: MS
authors.lastname: Chang
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D017209:Apoptosis; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000378:metabolism*; D006801:Humans; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D050199:Podocytes / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; D001786:Blood Glucose; D018932:Chemokine CCL2; D007378:Interleukins; D018123:Receptors, Interleukin; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; C492510:interleukin-20 receptor; D020780:Matrix Metalloproteinase 9; C422042:interleukin 20