title: Protective role of small pigment epithelium-derived factor (PEDF) peptide in diabetic renal injury.
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.
authors.affiliation: 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.
authors.forename: Alaa S
authors.initials: AS
authors.lastname: Awad
authors.forename: Ting
authors.initials: T
authors.lastname: Gao
authors.forename: Anzor
authors.initials: A
authors.lastname: Gvritishvili
authors.forename: Hanning
authors.initials: H
authors.lastname: You
authors.forename: Yanling
authors.initials: Y
authors.lastname: Liu
authors.forename: Timothy K
authors.initials: TK
authors.lastname: Cooper
authors.forename: W Brian
authors.initials: WB
authors.lastname: Reeves
authors.forename: Joyce
authors.initials: J
authors.lastname: Tombran-Tink
mesh_terms: D000419:Albuminuria / Q000517:prevention & control; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D005136:Eye Proteins / Q000502:physiology / Q000627:therapeutic use*; D007668:Kidney / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D008811:Mice, Inbred DBA; D009414:Nerve Growth Factors / Q000502:physiology / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000627:therapeutic use*; D050199:Podocytes / Q000187:drug effects; D015843:Serpins / Q000502:physiology / Q000627:therapeutic use*; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D008565:Membrane Proteins; D009414:Nerve Growth Factors; D010446:Peptide Fragments; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor; C113267:nephrin
keywords: diabetic nephropathy; pigment epithelium-derived factor; podocytes