Vitamin D/vitamin D receptor/Atg16L1 axis maintains podocyte autophagy and survival in diabetic kidney disease. Issue 1 (31st December 2022)

• Record Type: Journal Article
• Authors: Shi, Lang; Xiao, Chao; Zhang, Yafei; Xia, Yao; Zha, Hongchu; Zhu, Jiefu; Song, Zhixia
• Is Part Of: Renal failure. Volume 44:Issue 1(2022)
• Page Start: 694
• Page End: 705
• Publication Date: 2022-12-31
• Subjects: aVitD3 -- diabetic nephropathy -- podocyte -- autophagy -- VDR/Atg16L1 axis; Chronic renal failure -- Periodicals; Acute renal failure -- Periodicals; Uremia -- Periodicals; 616.614005
• DOI: 10.1080/0886022X.2022.2063744
• Languages: English
• ISSNs: 0886-022X

Abstract

Abstract: Objective: To investigate the effect of vitamin D/vitamin D receptor (VDR)/Atg16L1 signaling on podocyte autophagy and survival in diabetic nephropathy. Methods: Diabetic rat models were induced by intraperitoneal injection of streptozotocin (STZ) (60 mg/kg) and treated with and without gavage of 0.1 μg/kg/d active vitamin D3 (aVitD3; 1, 25- OH vitamin D3) and kidney tissues assessed by histopathology and immunohistochemistry. The murine podocyte cell line MPC-5 was cultured under hyperglycemic conditions in the absence or presence of 100 nmol/L calcitriol to investigate podocyte injury and autophagy. Cell survival rates were analyzed using Cell Counting Kit-8 (CCK-8) assays and the numbers of autophagosomes were determined after transduction with the mRFP-GFP-LC3 autophagy reporter construct. The expression of autophagy-related proteins (LC3-II, beclin-1, Atg16L1) and podocyte-related proteins (nephrin, podocin, synaptopodin, and desmin) was determined by Western blotting. Results: VDR expression and autophagy were decreased in diabetic nephropathy. Calcitriol treatment repressed renal injury in rat diabetic kidneys and reduced high glucose-induced damage to cultured podocytes. Mechanistically, Atg16L1 was identified as a functional target of VDR, and siRNA-mediated knockdown of VDR and Atg16L1 blocked the protective effects of aVitD3 against podocyte damage. Conclusion: Autophagy protects podocytes from damage in DN and is modulated by VitD3/VDR signaling and downstream regulation of Atg16L1 expression.