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Receptor-associated prorenin system contributes to development of inflammation and angiogenesis in proliferative
Atsuhiro Kanda1, Susumu Ishida1
1Laboratory of Ocular Cell Biology and Visual Science, Department of Ophthalmology, Hokkaido University Graduate School of Medicine, N-15, W-7, Kita-ku, Sapporo, Hokkaido 060-8638 Japan.
Abstract:
The renin-angiotensin system (RAS) plays a potential role in the development of end-organ damage, and tissue RAS activation has been suggested as a risk factor of several diseases including diabetes. So far, using animal disease models, we have shown molecular mechanisms, in which tissue RAS stimulates retinal angiogenesis, and the critical roles of (pro)renin receptor [(P)RR] in retinal RAS activation and its concurrent intracellular signal transduction, referred to as the receptor-associated prorenin system (RAPS). Moreover, we recently reported that the protein levels of prorenin and soluble (P)RR increased in the vitreous fluids obtained from patients with proliferative diabetic retinopathy (PDR), suggesting the association of (P)RR with vascular endothelial growth factor (VEGF)-driven angiogenic activity in human PDR, and also showed a close relationship between the vitreous renin activity and VEGF-induced pathogenesis of diabetic retinopathy. Our data using animal disease models and human clinical samples suggest that both vitreous RAS and retinal RAPS play critical roles in the molecular pathogenesis of diabetic retinopathy.
Insights
The renin-angiotensin system (RAS) and (pro)renin receptor [(P)RR] are implicated in diabetic retinopathy. Vitreous RAS and retinal receptor-associated prorenin system (RAPS) activation contribute to disease development.
Area of Science:
- Ophthalmology
- Endocrinology
- Molecular Biology
Background:
- The renin-angiotensin system (RAS) is linked to end-organ damage and diseases like diabetes.
- Tissue RAS activation is a potential risk factor for various diseases.
- The (pro)renin receptor [(P)RR] and its associated pathways are implicated in cellular signaling.
Purpose of the Study:
- To investigate the role of tissue RAS and (P)RR in diabetic retinopathy.
- To elucidate the molecular mechanisms of retinal angiogenesis in diabetes.
- To examine the association of (P)RR and vitreous renin activity with proliferative diabetic retinopathy (PDR).
Main Methods:
- Utilized animal disease models to study retinal angiogenesis and RAS activation.
- Analyzed vitreous fluids from PDR patients for prorenin and soluble (P)RR levels.
- Correlated vitreous renin activity with VEGF-induced pathogenesis.
Main Results:
- Demonstrated that tissue RAS stimulates retinal angiogenesis via (P)RR and receptor-associated prorenin system (RAPS).
- Found increased prorenin and soluble (P)RR in vitreous fluids of PDR patients.
- Established a link between vitreous renin activity, VEGF, and diabetic retinopathy pathogenesis.
Conclusions:
- Both vitreous RAS and retinal RAPS play critical roles in the molecular pathogenesis of diabetic retinopathy.
- (P)RR is associated with VEGF-driven angiogenic activity in human PDR.
- These findings highlight potential therapeutic targets for diabetic retinopathy.
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