Protective role of small pigment epithelium-derived factor (PEDF) peptide in diabetic renal injury

Alaa S. Awad, Ting Gao, Anzor Gvritishvili, Hanning You, Yanling Liu, Timothy K. Cooper, W. Brian Reeves, Joyce Tombran-Tink

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Pigment epithelium-derived factor (PEDF) is a multifunctional protein with antiangiogenic, antioxidative, and anti-inflammatory properties. PEDF is involved in the pathogenesis of diabetic retinopathy, but its direct role in the kidneys remains unclear. We hypothesize that a PEDF fragment (P78-PEDF) confers kidney protection in diabetic nephropathy (DN). The localization of the full-length PEDF protein were determined in DBA mice following multiple low doses of streptozotocin. Using immunohistochemistry, PEDF was localized in the kidney vasculature, interstitial space, glomeruli, tubules, and renal medulla. Kidney PEDF protein and mRNA expression were significantly reduced in diabetic mice. Continuous infusion of P78-PEDF for 6 wk resulted in protection from diabetic neuropathy as indicated by reduced albuminuria and blood urea nitrogen, increased nephrin expression, decreased kidney macrophage recruitment and inflammatory cytokines, and reduced histological changes compared with vehicle-treated diabetic mice. In vitro, P78-PEDF blocked the increase in podocyte permeability to albumin and disruption of the actin cytoskeleton induced by puromycin aminonucleoside treatment. These findings highlight the importance of P78-PEDF peptide as a potential therapeutic modality in early phase diabetic renal injury.

Original languageEnglish (US)
Pages (from-to)F891-F900
JournalAmerican Journal of Physiology - Renal Physiology
Volume305
Issue number6
DOIs
StatePublished - Sep 15 2013
Externally publishedYes

Keywords

  • Diabetic nephropathy
  • Pigment epithelium-derived factor
  • Podocytes

ASJC Scopus subject areas

  • Physiology
  • Urology

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