Hsu Yu-Hsiang, Li Hsing-Hui, Sung Junne-Ming, Chen Wei-Yu, Hou Ya-Chin, Weng Yun-Han, Lai Wei-Ting, Wu Chih-Hsing, Chang Ming-Shi
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.
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.
白细胞介素（IL）-20是IL-10家族的一种促炎细胞因子，参与急性和慢性肾衰竭。本研究的目的是阐明IL-20在糖尿病肾病发展过程中的作用。我们发现，在链脲佐菌素诱导的糖尿病小鼠和大鼠的肾脏中，IL-20及其受体IL-20R1上调。在体外，IL-20诱导足细胞中基质金属蛋白酶-9（MMP-9）、单核细胞趋化蛋白-1（MCP-1）、转化生长因子-β1（TGF-β1）和血管内皮生长因子（VEGF）的表达。过氧化氢、高剂量葡萄糖和TGF-β1可上调IL-20。此外，IL-20通过激活半胱天冬酶-8诱导足细胞凋亡。在链脲佐菌素诱导的早期糖尿病肾病中，IL-20R1缺陷小鼠的血糖和血清尿素氮水平较低，肾小球面积比野生型对照小鼠小。抗IL-20单克隆抗体（7E）治疗可降低链脲佐菌素诱导的糖尿病肾病早期小鼠的血糖和肾小球面积，并改善肾功能。酶联免疫吸附测定（ELISA）显示，糖尿病患者血清IL-20水平高于健康对照者。本研究结果表明，IL-20诱导足细胞凋亡，并在早期糖尿病肾病的发病机制中起作用。
