Renoprotective role of the vitamin D receptor in diabetic nephropathy

Z. Zhang, L. Sun, Y. Wang, G. Ning, A. W. Minto, J. Kong, R. J. Quigg, Y. C. Li

Research output: Contribution to journalArticle

231 Scopus citations

Abstract

1,25-Dihydroxyvitamin D3 negatively regulates the renin-angiotensin system (RAS), which plays a critical role in the development of diabetic nephropathy. We tested if mice lacking the vitamin D receptor (VDR) are more susceptible to hyperglycemia-induced renal injury. Diabetic VDR knockout mice developed more severe albuminuria and glomerulosclerosis due to increased glomerular basement membrane thickening and podocyte effacement. More fibronectin (FN) and less nephrin were expressed in the VDR knockout mice compared to diabetic wild-type mice. In receptor knockout mice, increased renin, angiotensinogen, transforming growth factor-β (TGF-β), and connective tissue growth factor accompanied the more severe renal injury. 1,25-Dihydroxyvitmain D3 inhibited high glucose (HG)-induced FN production in cultured mesangial cells and increased nephrin expression in cultured podocytes. 1,25-Dihydroxyvitmain D3 also suppressed HG-induced activation of the RAS and TGF-β in mesangial and juxtaglomerular cells. Our study suggests that receptor-mediated vitamin D actions are renoprotective in diabetic nephropathy.

Original languageEnglish (US)
Pages (from-to)163-171
Number of pages9
JournalKidney International
Volume73
Issue number2
DOIs
StatePublished - Jan 10 2008
Externally publishedYes

Keywords

  • Albuminuria
  • Diabetic nephropathy
  • Glomerulosclerosis
  • Reninangiotensin system
  • Vitamin D
  • Vitamin D receptor

ASJC Scopus subject areas

  • Nephrology

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  • Cite this

    Zhang, Z., Sun, L., Wang, Y., Ning, G., Minto, A. W., Kong, J., Quigg, R. J., & Li, Y. C. (2008). Renoprotective role of the vitamin D receptor in diabetic nephropathy. Kidney International, 73(2), 163-171. https://doi.org/10.1038/sj.ki.5002572