IMR Press / FBL / Volume 13 / Issue 10 / DOI: 10.2741/2976

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Pathologic roles of prorenin and (pro)renin receptor in the eye
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1 Laboratory of Retinal Cell Biology, Keio University School of Medicine, Tokyo, Japan
2 Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan,
3 Internal Medicine, Keio University School of Medicine, Tokyo, Japan

*Author to whom correspondence should be addressed.

Academic Editor: Atsuhiro Ichihara

Front. Biosci. (Landmark Ed) 2008, 13(10), 3884–3895; https://doi.org/10.2741/2976
Published: 1 May 2008
(This article belongs to the Special Issue Renin, prorenin, and prorenin receptor)
Abstract

Recent reports indicated that tissue renin-angiotensin system (RAS) was upregulated and angiotensin II type 1 receptor signaling plays crucial roles in ocular inflammation and neovascularization; however, the precise mechanism for activating tissue RAS had not been defined until recently. (Pro)renin receptor, a recently identified molecule existing in the major organs but not in the circulation, has attracted growing attention as an activator of tissue RAS. When the handle region of the prorenin prosegment binds to (pro)renin receptor, prorenin undergoes a conformational change to its enzymatically active state without the conventional proteolysis of the prorenin prosegment. Systemic treatment with a peptide with the structure of the handle region (handle region peptide; HRP), which competitively binds to (pro)renin receptor as a decoy peptide and inhibit the nonproteolytic activation of prorenin, resulted in the suppression of retinal inflammation and neovascularizaion in the rodent models. Retinal expression of RAS-related inflammatory and angiogenic molecules, such as intercellular adhesion molecule-1, monocyte chemotactic protein-1, and vascular endothelial growth factor, was also suppressed with application of HRP. These findings demonstrate that nonproteolytically activated prorenin plays a significant role in the ocular inflammation and neovascularization.

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