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- Title
Involvement of the Rho/Rho Kinase Signaling Pathway in Platelet-Derived Growth Factor BB-induced Vascular Endothelial Growth Factor Expression in Diabetic Rat Retina.
- Authors
Tamotsu Yokota; Kazunori Utsunomiya; Kanta Taniguchi; Atsushi Gojo; Hideaki Kurata; Naoko Tajima
- Abstract
Abstract Purpose To examine the role played by the Rho/Rho kinase pathway in the platelet-derived growth factor BB (PDGF-BB)-induced expression of vascular endothelial growth factor (VEGF) in the diabetic rat retina. Methods Male Sprague-Dawley rats were made diabetic by a single intraperitoneal injection of streptozotocin. Diabetic rats and PDGF-BB-exposed primary cultured porcine retinal pericyte cells (PRPCs) were treated with fluvastatin, an HMG-CoA reductase inhibitor, and fasudil, a selective Rho kinase inhibitor. The retinal expression of VEGF was determined by reverse transcriptase-polymerase chain reaction (RT-PCR). The mRNA expression of VEGF and the activation of Rho A were studied by Northern and Western blot analyses. Results RT-PCR showed that in rats that were diabetic for 4 weeks VEGF mRNA expression levels were 1.8-fold those in control rats. This enhanced expression was blocked by treatment with fluvastatin or fasudil. Exposure of PRPCs to PDGF-BB increased their VEGF mRNA expression threefold, and fluvastatin suppressed this effect. Fluvastatin also suppressed the PDGF-BB-induced activation of Rho GTPase in PRPCs. Conclusions The Rho/Rho kinase pathway may be involved in the upregulation of VEGF expression in the diabetic retina, suggesting that fasudil might be useful for the prevention of diabetic retinopathy. Jpn J Ophthalmol 2007;51:424–430 © Japanese Ophthalmological Society 2007
- Subjects
GROWTH factors; VASCULAR endothelial growth factors; RETINAL diseases; DIABETES; LABORATORY rats; STREPTOZOTOCIN; ANTINEOPLASTIC antibiotics
- Publication
Japanese Journal of Ophthalmology, 2007, Vol 51, Issue 6, p424
- ISSN
0021-5155
- Publication type
Article
- DOI
10.1007/s10384-007-0471-0