Involvement of the Rho/Rho kinase signaling pathway in platelet-derived growth factor BB-induced vascular endothelial growth factor expression in diabetic rat retina

• Published in: Japanese journal of ophthalmology Vol. 51; no. 6; pp. 424 - 430
• Main Authors: Yokota, Tamotsu, Utsunomiya, Kazunori, Taniguchi, Kanta, Gojo, Atsushi, Kurata, Hideaki, Tajima, Naoko
• Format: Journal Article
• Language: English
• Published: Japan Springer Nature B.V 01-11-2007
• Subjects: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - analogs & derivatives; 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - pharmacology; Angiogenesis Inducing Agents - pharmacology; Animals; Blotting, Northern; Blotting, Western; Cells, Cultured; Diabetes Mellitus, Experimental - genetics; Diabetes Mellitus, Experimental - metabolism; Diabetic Retinopathy - genetics; Diabetic Retinopathy - metabolism; Fatty Acids, Monounsaturated - pharmacology; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Indoles - pharmacology; Male; Pericytes - drug effects; Platelet-Derived Growth Factor - pharmacology; Protein Kinase Inhibitors - pharmacology; Proto-Oncogene Proteins c-sis; Rats; Rats, Sprague-Dawley; Retinal Vessels - cytology; Reverse Transcriptase Polymerase Chain Reaction; rho GTP-Binding Proteins - antagonists & inhibitors; rho GTP-Binding Proteins - physiology; rho-Associated Kinases - antagonists & inhibitors; rho-Associated Kinases - physiology; RNA, Messenger - metabolism; Signal Transduction - physiology; Swine; Up-Regulation - drug effects; Vascular Endothelial Growth Factor A - biosynthesis; Vascular Endothelial Growth Factor A - genetics
• ISSN: 0021-5155; 1613-2246
• DOI: 10.1007/s10384-007-0471-0

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.
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.
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.
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.