(Pro)renin receptor is associated with angiogenic activity in proliferative diabetic retinopathy.

Kanda, A.; Noda, K.; Saito, W.; Ishida, S.

(Pro)renin receptor is associated with angiogenic activity in proliferative diabetic retinopathy.

Kanda, A.; Noda, K.; Saito, W. et al.

Diabetologia, 2012, 55(11), 3104-3113

Permalink : https://hdl.handle.net/2115/52727

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アクセス権	open access
URI	https://hdl.handle.net/2115/52727
タイトル	(Pro)renin receptor is associated with angiogenic activity in proliferative diabetic retinopathy.
著者	Kanda, A. ; Noda, K. ; Saito, W. ; Ishida, S.
著者名 Kanda, A.
著者名 Noda, K.
著者名 Saito, W.
著者名 Ishida, S.
言語	英語
キーワード	Angiogenesis
	Diabetic retinopathy
	(Pro)renin receptor
	Receptor-associated prorenin system
	Renin–angiotensin system
	Vascular endothelial growth factor
発行日	2012-11
出版者	Berlin Springer Verlag
収録物名	Diabetologia
巻(号)	55(11)
ページ	3104-3113
抄録	AIMS/HYPOTHESIS: The renin-angiotensin system (RAS) potentially has a role in the development of end-organ damage, and tissue RAS activation has been suggested as a risk factor for diabetic retinopathy. We have recently shown significant involvement of (pro)renin receptor ([P]RR) in retinal inflammation in a rodent model of early diabetes. In this study we aim to elucidate the (P)RR-associated pathogenesis of fibrovascular proliferation, a late-stage angiogenic complication in human diabetic retinopathy. METHODS: Vitreous fluids from 23 eyes of patients with proliferative diabetic retinopathy (PDR) and 16 eyes of controls with non-diabetic, idiopathic macular diseases (macular hole and epiretinal membrane) were collected. Protein levels of soluble (P)RR were measured by ELISA, and immunofluorescence was performed to assess the localisation of (P)RR and related molecules in fibrovascular tissues from PDR eyes. RESULTS: (P)RR immunoreactivity was detected in neovascular endothelial cells, colocalised with prorenin, phosphorylated extracellular signal-regulated kinase (ERK) and vascular endothelial growth factor (VEGF). Prorenin application to human retinal microvascular endothelial cells significantly upregulated mRNA expression of VEGF, especially the VEGF165 isoform, which was abolished by (P)RR or ERK signalling blockade. Proteases known to cleave (P)RR, including furin, were positive in endothelial cells in fibrovascular tissues. Protein levels of soluble (P)RR in vitreous fluids were higher in PDR eyes than in non-diabetic control eyes, and correlated significantly with vitreous prorenin and VEGF levels and the vascular density of fibrovascular tissues. CONCLUSIONS/INTERPRETATION: Our data using human samples provide the first evidence that (P)RR is associated with angiogenic activity in PDR.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	The final publication is available at www.springerlink.com
PISSN	0012-186X
EISSN	1432-0428
NCID	AA00628104
関連情報	PMID 22930161
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1007/s00125-012-2702-2