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- Title
Administration of pigment epithelium-derived factor (PEDF) reduces proteinuria by suppressing decreased nephrin and increased VEGF expression in the glomeruli of adriamycin-injected rats.
- Authors
Toshiko Fujimura; Sho-ichi Yamagishi; Seiji Ueda; Kei Fukami; Ryo Shibata; Yuriko Matsumoto; Yusuke Kaida; Ayako Hayashida; Kiyomi Koike; Takanori Matsui; Kei-ichiro Nakamura; Seiya Okuda
- Abstract
Background. Pigment epithelium-derived factor (PEDF) is a glycoprotein with potent neuronal differentiating activity. We, along with others, have recently found that PEDF inhibits retinal hyperpermeability by counteracting the biological effects of vascular endothelial growth factor (VEGF). However, the protective role of PEDF against nephrotic syndrome (NS), a condition of hyperpermeability in the glomerular capillaries, remains to be elucidated. In this study, we investigated whether and how PEDF reduced proteinuria in rats with adriamycin (ADR)-induced nephropathy (ADN), an experimental model of NS. Methods. ADN was induced by a single intravenous injection of doxorubicin hydrochloride (n = 12). Half the ADN rats were intravenously administrated human recombinant PEDF; the other half were given vehicle everyday for up to 14 days. Control rats (n = 6) received vehicle only. Results. In ADN, expression levels of PEDF in isolated glomeruli were significantly decreased, which were associated with a marked proteinuria and increased urinary excretion of nephrin, an index of podocyte damage. Loss of nephrin and decreased podocyte cell number and fusion of foot processes of podocytes with nuclear factor-kappa B (NF-κB) activation and VEGF overexpression were also observed in the glomeruli of rats with ADN. Intravenous administration of PEDF ameliorated all of these changes in ADN rats. Conclusion. The present findings suggest that PEDF could reduce proteinuria by suppressing podocyte damage and decreased nephrin as well as increased VEGF expression in the glomeruli of ADN rats. Pharmacological up-regulation or substitution of PEDF may offer a promising therapeutic strategy for the treatment of nephrotic syndrome.
- Subjects
DRUG administration; GLYCOPROTEINS; PROTEINURIA; VASCULAR endothelial growth factors; KIDNEY glomerulus; DOXORUBICIN; LABORATORY rats; THERAPEUTICS
- Publication
Nephrology Dialysis Transplantation, 2009, Vol 24, Issue 5, p1397
- ISSN
0931-0509
- Publication type
Article
- DOI
10.1093/ndt/gfn659