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CCRL2 Modulates Physiological and Pathological Angiogenesis During Retinal Development
Chemerin is a multifunctional protein involved in the regulation of inflammation, metabolism, and tumorigenesis. It binds to three receptors, CMKLR1, GPR1 and CCRL2. CMKLR1 is a fully functional receptor mediating most of the known activities of chemerin. CCRL2 does not seem to couple to any intrace...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8733553/ https://www.ncbi.nlm.nih.gov/pubmed/35004698 http://dx.doi.org/10.3389/fcell.2021.808455 |
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author | Ben Dhaou, Cyrine Del Prete, Annalisa Sozzani, Silvano Parmentier, Marc |
author_facet | Ben Dhaou, Cyrine Del Prete, Annalisa Sozzani, Silvano Parmentier, Marc |
author_sort | Ben Dhaou, Cyrine |
collection | PubMed |
description | Chemerin is a multifunctional protein involved in the regulation of inflammation, metabolism, and tumorigenesis. It binds to three receptors, CMKLR1, GPR1 and CCRL2. CMKLR1 is a fully functional receptor mediating most of the known activities of chemerin. CCRL2 does not seem to couple to any intracellular signaling pathway and is presently considered as an atypical receptor able to present the protein to cells expressing CMKLR1. CCRL2 is expressed by many cell types including leukocyte subsets and endothelial cells, and its expression is strongly upregulated by inflammatory stimuli. We recently reported that chemerin can negatively regulate the angiogenesis process, including during the development of the vascular network in mouse retina. The role of CCRL2 in angiogenesis was unexplored so far. In the present work, we demonstrate that mice lacking CCRL2 exhibit a lower density of vessels in the developing retina and this phenotype persists in adulthood, in a CMKLR1-dependent manner. Vascular sprouting was not affected, while vessel pruning, and endothelial cell apoptosis were increased. Pathological angiogenesis was also reduced in CCRL2(-/-) mice in a model of oxygen-induced retinopathy. The phenotype closely mimics that of mice overexpressing chemerin, and the concentration of chemerin was found elevated in the blood of newborn mice, when the retinal vasculature develops. CCRL2 appears therefore to regulate the distribution and concentration of chemerin in organs, regulating thereby its bioactivity. |
format | Online Article Text |
id | pubmed-8733553 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87335532022-01-07 CCRL2 Modulates Physiological and Pathological Angiogenesis During Retinal Development Ben Dhaou, Cyrine Del Prete, Annalisa Sozzani, Silvano Parmentier, Marc Front Cell Dev Biol Cell and Developmental Biology Chemerin is a multifunctional protein involved in the regulation of inflammation, metabolism, and tumorigenesis. It binds to three receptors, CMKLR1, GPR1 and CCRL2. CMKLR1 is a fully functional receptor mediating most of the known activities of chemerin. CCRL2 does not seem to couple to any intracellular signaling pathway and is presently considered as an atypical receptor able to present the protein to cells expressing CMKLR1. CCRL2 is expressed by many cell types including leukocyte subsets and endothelial cells, and its expression is strongly upregulated by inflammatory stimuli. We recently reported that chemerin can negatively regulate the angiogenesis process, including during the development of the vascular network in mouse retina. The role of CCRL2 in angiogenesis was unexplored so far. In the present work, we demonstrate that mice lacking CCRL2 exhibit a lower density of vessels in the developing retina and this phenotype persists in adulthood, in a CMKLR1-dependent manner. Vascular sprouting was not affected, while vessel pruning, and endothelial cell apoptosis were increased. Pathological angiogenesis was also reduced in CCRL2(-/-) mice in a model of oxygen-induced retinopathy. The phenotype closely mimics that of mice overexpressing chemerin, and the concentration of chemerin was found elevated in the blood of newborn mice, when the retinal vasculature develops. CCRL2 appears therefore to regulate the distribution and concentration of chemerin in organs, regulating thereby its bioactivity. Frontiers Media S.A. 2021-12-23 /pmc/articles/PMC8733553/ /pubmed/35004698 http://dx.doi.org/10.3389/fcell.2021.808455 Text en Copyright © 2021 Ben Dhaou, Del Prete, Sozzani and Parmentier. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Ben Dhaou, Cyrine Del Prete, Annalisa Sozzani, Silvano Parmentier, Marc CCRL2 Modulates Physiological and Pathological Angiogenesis During Retinal Development |
title | CCRL2 Modulates Physiological and Pathological Angiogenesis During Retinal Development |
title_full | CCRL2 Modulates Physiological and Pathological Angiogenesis During Retinal Development |
title_fullStr | CCRL2 Modulates Physiological and Pathological Angiogenesis During Retinal Development |
title_full_unstemmed | CCRL2 Modulates Physiological and Pathological Angiogenesis During Retinal Development |
title_short | CCRL2 Modulates Physiological and Pathological Angiogenesis During Retinal Development |
title_sort | ccrl2 modulates physiological and pathological angiogenesis during retinal development |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8733553/ https://www.ncbi.nlm.nih.gov/pubmed/35004698 http://dx.doi.org/10.3389/fcell.2021.808455 |
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