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Hypoxia decreases podocyte expression of slit diaphragm proteins

Authors Lu H, Kapur G, Mattoo, Lyman

Received 14 October 2011

Accepted for publication 23 December 2011

Published 18 July 2012 Volume 2012:5 Pages 101—107

DOI https://doi.org/10.2147/IJNRD.S27332

Review by Single-blind

Peer reviewer comments 5


Hong Lu,1 Gaurav Kapur,1 Tej K Mattoo,1 William D Lyman1,2

1Carman and Ann Adams Department of Pediatrics, 2Children's Research Center of Michigan, Children's Hospital of Michigan, Detroit, MI, USA

Background: Chronic hypoxia contributes to progressive tubulointerstitial injury and, consequently, renal failure. However, the effect of hypoxia on glomerular podocytes, which are integral to the slit diaphragm complex and responsible for selectivity of the glomerular filtration barrier, has not been completely determined.
Methods: Conditionally immortalized mouse podocyte cells were exposed to hypoxic (1% O2) or normoxic (room air) conditions for 24, 48, or 72 hours, after which cell viability was determined by MTT assay. Cells were stained with podocin and phalloidin to determine podocin and intracellular actin distribution. Expression of synaptopodin, CD2-associated protein (CD2AP), NcK, transforming growth factor-β1 (TGF-β1), hypoxia-inducible factor (HIF-1α) were evaluated by real-time polymerase chain reaction.
Results: Podocytes exposed to hypoxia had significantly reduced viability at 48 (87%) and 72 hours (66%). There was disarrangement of intracellular filament actin by phalloidin staining, a 30% weaker fluorescence intensity by podocin staining, significantly reduced expression of synaptopodin (12%), CD2AP (42%), NcK (38%), and increased expression of TGF-β1 and P-ERK after hypoxia treatment.
Conclusion: Podocyte exposure to hypoxia leads to reduced viability and SD protein expression, which may explain persistent and/or increasing proteinuria in patients with progressive renal failure. Increased expression of TGF-β1 and P-ERK is associated with apoptosis and fibrosis, which could be the link between hypoxia and glomerular injury.

Keywords: podocytes, hypoxia, slit-diaphragm proteins

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