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Am J Physiol Renal Physiol. 2013 Sep 15;305(6):F891-900. doi: 10.1152/ajprenal.00149.2013. Epub 2013 Jul 24.

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

Author information

1
Associate Professor of Medicine, and Cellular & Molecular Physiology, Penn State Univ., Hershey Medical Center, College of Medicine, Division of Nephrology, H040, 500 Univ. Drive, P.O. Box 850, BMR Bldg., C5830, Hershey, PA 17033. asa17@psu.edu.

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.

KEYWORDS:

diabetic nephropathy; pigment epithelium-derived factor; podocytes

PMID:
23884140
PMCID:
PMC3761290
DOI:
10.1152/ajprenal.00149.2013
[Indexed for MEDLINE]
Free PMC Article

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