title: [(Pro) renin receptor in the pathogenesis of proliferative diabetic retinopathy].
abstract: The renin-angiotensin system (RAS), originally regarded as an important controller of systemic blood pressure (circulatory RAS), plays a pivotal role in pathological vascular conditions including inflammation and angiogenesis (tissue RAS). (Pro) renin receptor [(P) RR] is known to bind with prorenin causing the dual activation of tissue renin-angiotensin system (RAS) together with RAS-independent intracellular signaling pathways and contributes to the molecular pathogenesis of end-organ damage. In this review, we investigated localization and expression of (P)RR in fibrovascular tissues and vitreous fluids from patients with proliferative diabetic retinopathy and evaluated the molecular mechanisms in vitro in order to confirm the conclusions regarding (P) RR from animal studies. (P)RR immunoreactivity was detected in vascular endothelial cells, co-localized with prorenin, phosphorylated extracellular signal-regulated kinase and vascular endothelial growth factor (VEGF). Protein levels of soluble (P) RR in the vitreous fluids were higher in proliferative diabetic retinopathy (PDR) eyes than in non-diabetic control eyes, and were significantly correlated with vitreous VEGF levels and the vascular density of fibrovascular tissues. We herein report the first evidence that shows the close association of (P) RR with angiogenic activity in human PDR. The present data suggest the validity of (P) RR as a molecular target for the treatment of PDR.
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Kanda
mesh_terms: D049109:Cell Proliferation; D003930:Diabetic Retinopathy / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009389:Neovascularization, Pathologic; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012083:Renin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism*; D000093342:Prorenin Receptor
chemical_list: D011956:Receptors, Cell Surface; D012083:Renin; D025262:Vacuolar Proton-Translocating ATPases; C458319:ATP6AP2 protein, human; D000093342:Prorenin Receptor