IL-17 deficiency aggravates the streptozotocin‐induced diabetic nephropathy through the reduction of autophagosome formation in mice

Molecular Medicine

Shanika Karunasagara¹  Kyung-Hyun Kim¹  Geum-Lan Hong¹  Ju-Young Jung¹  Da-Young Jung¹  Won-Il Jeong² 

[1] Department of Veterinary Medicine, Institute of Veterinary Science, Chungnam National University, 99, Daehak-ro, Yuseong-gu, 34134, Daejeon, Republic of Korea;Laboratory of Liver Research, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, 34141, Daejeon, Republic of Korea;

关键词: IL-17A;    Diabetic nephropathy;    Autophagy;    Autophagosome formation;   

DOI  :  10.1186/s10020-021-00285-4

来源: Springer

【 摘 要 】

BackgroundDiabetic nephropathy (DN) is one of the most important medical complications of diabetes mellitus. Autophagy is an important mediator of pathological response and plays a critical role in inflammation during the progression of diabetic nephropathy. Interleukin (IL)-17A favorably modulates inflammatory disorders including DN. In this study, we examined whether IL-17A deficiency affected the autophagy process in the kidneys of mice with streptozotocin (STZ)-induced DN.MethodsThe autophagic response of IL-17A to STZ-induced nephrotoxicity was evaluated by analyzing STZ-induced functional and histological renal injury in IL-17A knockout (KO) mice.ResultsIL-17A KO STZ-treated mice developed more severe nephropathy than STZ-treated wild-type (WT) mice, with increased glomerular damage and renal interstitial fibrosis at 12 weeks. IL-17A deficiency also increased the up-regulation of proinflammatory cytokines and fibrotic gene expression after STZ treatment. Meanwhile, autophagy-associated proteins were induced in STZ-treated WT mice. However, IL-17A KO STZ-treated mice displayed a significant decrease in protein expression. Especially, the levels of LC3 and ATG7, which play crucial roles in autophagosome formation, were notably decreased in the IL-17A KO STZ-treated mice compared with their WT counterparts.ConclusionsIL-17 deficiency aggravates of STZ-induced DN via attenuation of autophagic response. Our study demonstrated that IL-17A mediates STZ-induced renal damage and represents a potential therapeutic target in DN.

【 授权许可】

CC BY