Cargando…
Involvement of Bradykinin B2 Receptor in Pathological Vascularization in Oxygen-Induced Retinopathy in Mice and Rabbit Cornea
The identification of components of the kallikrein–kinin system in the vitreous from patients with microvascular retinal diseases suggests that bradykinin (BK) signaling may contribute to pathogenesis of retinal vascular complications. BK receptor 2 (B2R) signaling has been implicated in both pro-in...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5855552/ https://www.ncbi.nlm.nih.gov/pubmed/29360776 http://dx.doi.org/10.3390/ijms19020330 |
_version_ | 1783307123249119232 |
---|---|
author | Terzuoli, Erika Morbidelli, Lucia Nannelli, Ginevra Giachetti, Antonio Donnini, Sandra Ziche, Marina |
author_facet | Terzuoli, Erika Morbidelli, Lucia Nannelli, Ginevra Giachetti, Antonio Donnini, Sandra Ziche, Marina |
author_sort | Terzuoli, Erika |
collection | PubMed |
description | The identification of components of the kallikrein–kinin system in the vitreous from patients with microvascular retinal diseases suggests that bradykinin (BK) signaling may contribute to pathogenesis of retinal vascular complications. BK receptor 2 (B2R) signaling has been implicated in both pro-inflammatory and pro-angiogenic effects promoted by BK. Here, we investigated the role of BK/B2R signaling in the retinal neovascularization in the oxygen-induced retinopathy (OIR) model. Blockade of B2R signaling by the antagonist fasitibant delayed retinal vascularization in mouse pups, indicating that the retinal endothelium is a target of the BK/B2R system. In the rabbit cornea assay, a model of pathological neoangiogenesis, the B2 agonist kallidin induced vessel sprouting and promoted cornea opacity, a sign of edema and tissue inflammation. In agreement with these results, in the OIR model, a blockade of B2R signaling significantly reduced retinal neovascularization, as determined by the area of retinal tufts, and, in the retinal vessel, it also reduced vascular endothelial growth factor and fibroblast growth factor-2 expression. All together, these findings show that B2R blockade reduces retinal neovascularization and inhibits the expression of proangiogenic and pro-inflammatory cytokines, suggesting that targeting B2R signaling may be an effective strategy for treating ischemic retinopathy. |
format | Online Article Text |
id | pubmed-5855552 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-58555522018-03-20 Involvement of Bradykinin B2 Receptor in Pathological Vascularization in Oxygen-Induced Retinopathy in Mice and Rabbit Cornea Terzuoli, Erika Morbidelli, Lucia Nannelli, Ginevra Giachetti, Antonio Donnini, Sandra Ziche, Marina Int J Mol Sci Article The identification of components of the kallikrein–kinin system in the vitreous from patients with microvascular retinal diseases suggests that bradykinin (BK) signaling may contribute to pathogenesis of retinal vascular complications. BK receptor 2 (B2R) signaling has been implicated in both pro-inflammatory and pro-angiogenic effects promoted by BK. Here, we investigated the role of BK/B2R signaling in the retinal neovascularization in the oxygen-induced retinopathy (OIR) model. Blockade of B2R signaling by the antagonist fasitibant delayed retinal vascularization in mouse pups, indicating that the retinal endothelium is a target of the BK/B2R system. In the rabbit cornea assay, a model of pathological neoangiogenesis, the B2 agonist kallidin induced vessel sprouting and promoted cornea opacity, a sign of edema and tissue inflammation. In agreement with these results, in the OIR model, a blockade of B2R signaling significantly reduced retinal neovascularization, as determined by the area of retinal tufts, and, in the retinal vessel, it also reduced vascular endothelial growth factor and fibroblast growth factor-2 expression. All together, these findings show that B2R blockade reduces retinal neovascularization and inhibits the expression of proangiogenic and pro-inflammatory cytokines, suggesting that targeting B2R signaling may be an effective strategy for treating ischemic retinopathy. MDPI 2018-01-23 /pmc/articles/PMC5855552/ /pubmed/29360776 http://dx.doi.org/10.3390/ijms19020330 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Terzuoli, Erika Morbidelli, Lucia Nannelli, Ginevra Giachetti, Antonio Donnini, Sandra Ziche, Marina Involvement of Bradykinin B2 Receptor in Pathological Vascularization in Oxygen-Induced Retinopathy in Mice and Rabbit Cornea |
title | Involvement of Bradykinin B2 Receptor in Pathological Vascularization in Oxygen-Induced Retinopathy in Mice and Rabbit Cornea |
title_full | Involvement of Bradykinin B2 Receptor in Pathological Vascularization in Oxygen-Induced Retinopathy in Mice and Rabbit Cornea |
title_fullStr | Involvement of Bradykinin B2 Receptor in Pathological Vascularization in Oxygen-Induced Retinopathy in Mice and Rabbit Cornea |
title_full_unstemmed | Involvement of Bradykinin B2 Receptor in Pathological Vascularization in Oxygen-Induced Retinopathy in Mice and Rabbit Cornea |
title_short | Involvement of Bradykinin B2 Receptor in Pathological Vascularization in Oxygen-Induced Retinopathy in Mice and Rabbit Cornea |
title_sort | involvement of bradykinin b2 receptor in pathological vascularization in oxygen-induced retinopathy in mice and rabbit cornea |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5855552/ https://www.ncbi.nlm.nih.gov/pubmed/29360776 http://dx.doi.org/10.3390/ijms19020330 |
work_keys_str_mv | AT terzuolierika involvementofbradykininb2receptorinpathologicalvascularizationinoxygeninducedretinopathyinmiceandrabbitcornea AT morbidellilucia involvementofbradykininb2receptorinpathologicalvascularizationinoxygeninducedretinopathyinmiceandrabbitcornea AT nannelliginevra involvementofbradykininb2receptorinpathologicalvascularizationinoxygeninducedretinopathyinmiceandrabbitcornea AT giachettiantonio involvementofbradykininb2receptorinpathologicalvascularizationinoxygeninducedretinopathyinmiceandrabbitcornea AT donninisandra involvementofbradykininb2receptorinpathologicalvascularizationinoxygeninducedretinopathyinmiceandrabbitcornea AT zichemarina involvementofbradykininb2receptorinpathologicalvascularizationinoxygeninducedretinopathyinmiceandrabbitcornea |