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High-glucose and advanced glycosylation end products increased podocyte permeability via PI3-K/Akt signaling.

Authors: Ha, TS 
Citation: Ha TS J Mol Med (Berl). 2010 Apr;88(4):391-400. doi: 10.1007/s00109-009-0575-8. Epub 2010 Jan 8.
Pubmed: (View Article at PubMed) PMID:20054520
DOI: Full-text: DOI:10.1007/s00109-009-0575-8

Regardless of the underlying disease, the proteinuric condition demonstrates ultrastructural changes in podocytes with retraction and effacement of the highly specialized interdigitating foot processes. To investigate how high-glucose (HG) and advanced glycosylation end products (AGE) induce podocyte phenotypical changes, including quantitative and distributional changes of zonula occludens (ZO)-1 protein and search for the signaling mechanisms, we cultured rat glomerular epithelial cells (GEpC) and mouse podocytes under: (1) normal glucose (5 mM, control); (2) HG (30 mM); (3) AGE-added; or (4) HG plus AGE-added conditions. HG plus AGE increased the permeability of monolayered GEpCs and induced ultrastructural separation between confluent GEpCs. ZO-1 moved to inner actin filament complexes in both AGE- and/or HG by confocal imaging. HG plus AGE-added condition also decreased ZO-1 protein amount and mRNA expression compared to normal glucose or osmotic control conditions. We could also confirm the induction of RAGE (receptor for AGE) and PI3-K/Akt signaling pathway by AGE and HG. In addition, LY294002, a PI3-K inhibitor, could prevent the quantitative and distributional changes of ZO-1 and RAGE and the increased permeability induced by HG and AGE. These findings suggest that diabetic conditions induce the podocyte ZO-1 changes via RAGE and PI3-K/Akt signaling, leading to increased permeability.


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CRRD Object Information
CRRD ID: 7244147
Created: 2013-05-22
Species: All species
Last Modified: 2013-05-22
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.