| First Author | Satofuka S | Year | 2009 |
| Journal | Diabetes | Volume | 58 |
| Issue | 7 | Pages | 1625-33 |
| PubMed ID | 19389828 | Mgi Jnum | J:154343 |
| Mgi Id | MGI:4367669 | Doi | 10.2337/db08-0254 |
| Citation | Satofuka S, et al. (2009) (Pro)renin receptor-mediated signal transduction and tissue renin-angiotensin system contribute to diabetes-induced retinal inflammation. Diabetes 58(7):1625-33 |
| abstractText | OBJECTIVE: The term 'receptor-associated prorenin system' (RAPS) refers to the pathogenic mechanisms whereby prorenin binding to its receptor dually activates the tissue renin-angiotensin system (RAS) and RAS-independent intracellular signaling via the receptor. The aim of the present study was to define the association of the RAPS with diabetes-induced retinal inflammation. RESEARCH DESIGN AND METHODS: Long-Evans rats, C57BL/6 mice, and angiotensin II type 1 receptor (AT1-R)-deficient mice with streptozotocin-induced diabetes were treated with (pro)renin receptor blocker (PRRB). Retinal mRNA expression of prorenin and the (pro)renin receptor was examined by quantitative RT-PCR. Leukocyte adhesion to the retinal vasculature was evaluated with a concanavalin A lectin perfusion-labeling technique. Retinal protein levels of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule (ICAM)-1 were examined by ELISA. Retinal extracellular signal-regulated kinase (ERK) activation was analyzed by Western blotting. RESULTS: Induction of diabetes led to significant increase in retinal expression of prorenin but not the (pro)renin receptor. Retinal adherent leukocytes were significantly suppressed with PRRB. Administration of PRRB inhibited diabetes-induced retinal expression of VEGF and ICAM-1. To clarify the role of signal transduction via the (pro)renin receptor in the diabetic retina, we used AT1-R-deficient mice in which the RAS was deactivated. Retinal adherent leukocytes in AT1-R-deficient diabetic mice were significantly suppressed with PRRB. PRRB suppressed the activation of ERK and the production of VEGF, but not ICAM-1, in AT1-R-deficient diabetic mice. CONCLUSIONS: These results indicate a significant contribution of the RAPS to the pathogenesis of diabetes-induced retinal inflammation, suggesting the possibility of the (pro)renin receptor as a novel molecular target for the treatment of diabetic retinopathy. |
