Hypoxia decreases podocyte expression of slit diaphragm proteins

Hong Lu, Gaurav Kapur, Tej K. Mattoo, William D. Lyman

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

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% O 2) 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.

Original languageEnglish
Pages (from-to)101-107
Number of pages7
JournalInternational Journal of Nephrology and Renovascular Disease
Volume5
DOIs
StatePublished - Jul 17 2012

Keywords

  • Hypoxia
  • Podocytes
  • Slit-diaphragm proteins

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