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Involvement of the Rho/Rho Kinase Signaling Pathway in Platelet-Derived Growth Factor BB-induced Vascular Endothelial Growth Factor Expression in Diabetic Rat Retina

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Japanese Journal of Ophthalmology Aims and scope Submit manuscript

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

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Authors and Affiliations

  1. Division of Diabetes and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan

    Tamotsu Yokota, Kazunori Utsunomiya, Kanta Taniguchi, Atsushi Gojo, Hideaki Kurata & Naoko Tajima

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  1. Tamotsu Yokota
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  2. Kazunori Utsunomiya
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  3. Kanta Taniguchi
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  4. Atsushi Gojo
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  6. Naoko Tajima
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Correspondence to Tamotsu Yokota.

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Yokota, T., Utsunomiya, K., Taniguchi, K. et al. Involvement of the Rho/Rho Kinase Signaling Pathway in Platelet-Derived Growth Factor BB-induced Vascular Endothelial Growth Factor Expression in Diabetic Rat Retina. Jpn J Ophthalmol 51, 424–430 (2007). https://doi.org/10.1007/s10384-007-0471-0

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