Dexamethasone Inhibits Podocyte Apoptosis by Stabilizing the PI3K-Akt Signal PathwayReport as inadecuate

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BioMed Research InternationalVolume 2013 2013, Article ID 326986, 9 pages

Research ArticleDepartment of Pediatrics, Guangzhou First People-s Hospital, Affiliate to Guangzhou Medical College, Guangzhou, Guangdong 510180, China

Received 13 January 2013; Revised 16 March 2013; Accepted 28 March 2013

Academic Editor: George E. Plopper

Copyright © 2013 Yu-Shengyou and Yu Li. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Corticosteroids like dexamethasone DEX are well-established treatments for the glomerular disease that sustain renal function, at least in part, by protecting podocytes from apoptotic death. In this study, we found that PAN causes abnormal expression of the PI3K-binding protein CD2AP, reducing PI3K-Akt signaling and promoting podocyte apoptosis. In contrast, DEX restores CD2AP-PI3K-Akt-GSK3β signaling, which promotes the activity of antiapoptotic proteins and inhibits the activity of proapoptotic proteins. In addition, we also found that CD2AP was aberrantly colocalized with p85. Normal CD2AP mRNA expression and subcellular protein distribution were maintained in the PAN + DEX group, and DEX coapplication also reduced CD2AP-p85 colocalization. PAN evoked a concentration-dependent decrease in p-Akt and p-GSK3β expressions, with p-Akt expression reaching a nadir at 15 min and p-GSK3β expression at 30 min. DEX treatment induced a concentration-dependent reversal of PAN-induced p-Akt and p-GSK3β downregulation. The PI3K inhibitor LY294002 blocked p-Akt and p-GSK3β expressions in podocytes. Cells treated with PAN exhibited a significantly higher apoptosis rate than untreated or vehicle-treated cells. Furthermore, LY294002 exacerbated PAN-induced apoptosis. DEX cotreatment caused a significant concentration-dependent decrease in PAN-induced apoptosis. These results strongly suggest that DEX protects podocytes by stabilizing the expression and subcellular distribution of CD2AP and by maintaining the expression of phosphor-activated Akt and GSK3β.

Author: Yu-Shengyou and Yu Li



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