1,25-Dihydroxyvitamin D3 Prevents Puromycin Aminonucleoside-Induced Apoptosis of Glomerular Podocytes by Activating the Phosphatidylinositol 3-Kinase/Akt-Signaling PathwayXiao H.a, b · Shi W.a · Liu S.a · Wang W.a · Zhang B.a · Zhang Y.b · Xu L.a · Liang X.a · Liang Y.a
aDivision of Nephrology, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong and bDepartment of Nephrology, Taihe Hospital, Yunyang Medical College, Shiyan, PR China
Background: Accumulating evidence suggests that vitamin D and its analogs reduce proteinuria and slow the decline in kidney function in chronic kidney disease. Given a rich literature identifying podocyte apoptosis as an early step in the pathophysiological progression to proteinuria and glomerulosclerosis, we hypothesized that vitamin D protects podocytes from undergoing apoptosis. Methods: A rat model of podocyte apoptosis was created by a single intravenous injection of 100 mg·kg–1 puromycin aminonucleoside (PAN) and received either solvent or 1,25(OH)2D3 treatment. Proteinuria, podocyte apoptosis, the expression of nephrin protein and mRNA, TGF-β/Smad and phosphatidylinositol 3-kinase (PI3K)/Akt-signaling pathway were evaluated, respectively. Results: PAN induced massive proteinuria, serum creatinine elevation and podocyte apoptosis in PAN nephropathy rats, which was associated with the loss of nephrin, an adhesion molecule specific for the glomerular slit and the reduced of p-Akt/Akt ratio. Moreover, PAN induced foot process retraction, redistribution of nephrin and the activation of TGF-β/Smad-signaling pathway. Compared with PAN nephropathy rats, 1,25(OH)2D3 significantly prevented loss of nephrin, foot process retraction and podocyte apoptosis by stimulating Akt phosphorylation and suppressing TGF-β/Smad-signaling pathway. Conclusion: 1,25(OH)2D3 reduced the PAN-induced podocyte apoptosis and loss of nephrin in PAN nephropathy rat. The anti-apoptotic effects of 1,25(OH)2D3 on podocytes may be partly attributable to activation of a PI3K/Akt survival pathway.
© 2009 S. Karger AG, Basel
H.X. and W.S contributed equally to this study.
Received: August 18, 2008
Accepted: December 17, 2008
Published online: February 6, 2009
Number of Print Pages : 10
Number of Figures : 4, Number of Tables : 1, Number of References : 36
American Journal of Nephrology
Vol. 30, No. 1, Year 2009 (Cover Date: July 2009)
Journal Editor: Bakris G. (Chicago, Ill.)
ISSN: 0250-8095 (Print), eISSN: 1421-9670 (Online)
For additional information: http://www.karger.com/AJN