ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: SA-PO507

Molecular Mechanism of Regulatory Effect of Vitamin D Receptor on Mitophagy of Proximal Tubular Epithelial Cells in Diabetic Nephropathy

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Yang, Cheng, The Third Xiangya Hospital of Central South University, Changsha, China
  • Zhang, Hao, The Third Xiangya Hospital of Central South University, Changsha, China
Background

Vitamin D receptor (VDR) is a kind of nuclear transcription factor, which is widely expressed in proximal tubular epithelial cells (PTECs). Our previous study found that VDR has anti-inflammatory and anti-fibrotic effects. Given the previous evidence that the expression of VDR decreased in PTECs of DN patients and VDR can regulate the mitophagy, how VDR contribute to the development of renal tubulointerstitial mitophagy in diabetic nephropathy is not entirely clear. In this study, we tend to investigate the effect of VDR on mitophagy dysfunction in diabetic nephropathy and its molecular mechanism.

Methods

VDR-knockout mice in C57BL/6 background were generated and streptozotocin (STZ)-induced diabetic mice were used in these experiments. Mitophagy in the PTECs was observed by electron microscope, and the pathological changes of the kidneys were delineated by periodic acid–Schiff (PAS) staining. Immunohistochemistry and Western blotting were performed to identify the expression of VDR, Collagen 1, Fibrinogen, α-SMA,TGF-β, Drp1, mitofusin 2, Pink1 and Bnip3.

Results

1. The blood glucose of the mice was significantly increased in the first week after the injection of STZ. 16 weeks after STZ injection, PAS staining revealed the glomerulomegaly and renal tubular injury of diabetic mice, suggesting that STZ-induced diabetic mice were generated successfully. 2. The accumulation of collagen in glomeruli and tubulointerstitium revealed the occurrence of renal fibrosis in the STZ-induced mice. The expression of Collagen 1, Fibrinogen and α-SMA in wild-type diabetic mice was lower than that in VDR-KO diabetic mice, thus confirming the anti-fibrotic effect of VDR in the pathogenesis of DN. In the diabetic model induced by STZ, there is severer mitophagy dysfunction in VDR-KO mouse than that in the wide type diabetic mouse, which indicates that VDR may regulate the mitophagy in diabetic nephropathy.

Conclusion

VDR can control the renal fibrosis and the progression of diabetics by regulating the mitophagy. VDR overexpression may act as a new target for the prevention and treatment of DN.

Funding

  • Government Support - Non-U.S.