Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy (Apr 2021)

Vitamin D/VDR Protects Against Diabetic Kidney Disease by Restoring Podocytes Autophagy

  • Song Z,
  • Xiao C,
  • Jia X,
  • Luo C,
  • Shi L,
  • Xia R,
  • Zhu J,
  • Zhang S

Journal volume & issue
Vol. Volume 14
pp. 1681 – 1693

Abstract

Read online

Zhixia Song,1,* Chao Xiao,2,* Xiaoli Jia,2 Chunhua Luo,3 Lang Shi,1 Rong Xia,1 Jiefu Zhu,4 Shizhong Zhang2 1Department of Nephrology, The First Clinical Medical College of Three Gorges University, Center People’s Hospital of Yichang, Yichang, 443000, People’s Republic of China; 2Three Gorges University College of Medical Science, Yichang, 443000, People’s Republic of China; 3Department of Clinical Laboratory, The First Clinical Medical College of Three Gorges University, Center People’s Hospital of Yichang, Yichang, 443000, People’s Republic of China; 4Center of Nephrology and Dialysis, Transplantation, Renmin Hospital of Wuhan University, Wuchang, Hubei, 430060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jiefu Zhu; Shizhong Zhang Email [email protected]; [email protected]: The present study is to investigate the effect of vitamin D/Vitamin D Receptor (VDR) signaling on podocyte autophagy in diabetic nephropathy.Methods: Kidney tissue sections from patients with diabetic nephropathy and nontumor kidney were checked under electronic microscope and VDR immunohistochemistry. Diabetic rat models were induced by intraperitoneal injection of streptozotocin (STZ) (60 mg/kg). Calcitriol treatment was achieved by gavage at dose of 0.1μg/kg/d. Blood, urine and kidney tissue specimens were used for serum, urine biochemistry, histopathology and molecular biology testing. Podocyte cell line MPC-5 was cultured under hyperglycaemic conditions in the absence or presence of 100 nmol/L calcitriol to investigate podocyte injury and autophagy.Results: VDR and autophagosomes in podocytes were significantly decreased in renal biopsy from patients with diabetic nephropathy, compared to healthy kidney tissue. Rats with STZ treatment developed typical diabetic kidney disease with low VDR expression. Calcitriol, the active form of vitamin D, could activate VDR and attenuate diabetic nephropathy including proteinuria and glomerular sclerosis. Calcitriol treatment also alleviated the podocyte foot process fusion, reduced podocyte injury marker desmin and preserved slit diaphragms proteins in diabetic nephropathy. Reduced LC3II/I, Beclin-1 and elevated p62 in renal homogenate and reduced autophagosomes and LC3II in podocytes indicated podocytes autophagy impairment in diabetic nephropathy. Whereas calcitriol treatment restored podocyte autophagy activities. In cultured podocytes, the protective effect of calcitriol against high glucose induced podocyte injury could be abated by autophagy inhibitor chloroquine.Conclusion: Our study delivered the evidence that calcitriol/VDR signaling attenuated diabetic nephropathy and podocytes injury by restoring podocytes autophagy. This finding may have potential implication for exploring protective mechanisms of calcitriol/VDR in diabetic nephropathy.Keywords: vitamin D receptor, calcitriol, diabetic nephropathy, podocyte, autophagy

Keywords