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

• Main Authors: Kyung-Hyun Kim, Geum-Lan Hong, Da-Young Jung, Shanika Karunasagara, Won-Il Jeong, Ju-Young Jung
• Format: Article
• Language: English
• Published: BMC 2021-03-01
• Series: Molecular Medicine
• Subjects: IL-17A; Diabetic nephropathy; Autophagy; Autophagosome formation
• Online Access: https://doi.org/10.1186/s10020-021-00285-4

Abstract Background Diabetic 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. Methods The 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. Results IL-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. Conclusions IL-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.