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Regulatory mechanisms of Robo4 and their effects on angiogenesis

Roundabout4 (Robo4) is a transmembrane receptor that belongs to the Roundabout (Robo) family of axon guidance molecules. Robo4 is an endothelial-specific receptor that participates in endothelial cell migration, proliferation, and angiogenesis and the maintenance of vasculature homeostasis. The purp...

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Detalles Bibliográficos
Autores principales: Dai, Chang, Gong, Qiaoyun, Cheng, Yan, Su, Guanfang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6620384/
https://www.ncbi.nlm.nih.gov/pubmed/31160487
http://dx.doi.org/10.1042/BSR20190513
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author Dai, Chang
Gong, Qiaoyun
Cheng, Yan
Su, Guanfang
author_facet Dai, Chang
Gong, Qiaoyun
Cheng, Yan
Su, Guanfang
author_sort Dai, Chang
collection PubMed
description Roundabout4 (Robo4) is a transmembrane receptor that belongs to the Roundabout (Robo) family of axon guidance molecules. Robo4 is an endothelial-specific receptor that participates in endothelial cell migration, proliferation, and angiogenesis and the maintenance of vasculature homeostasis. The purpose of this review is to summarize and analyze three main mechanisms related to the expression and function of Robo4 during developmental and pathological angiogenesis. In this review, static shear stress and the binding of transcription factors such as E26 transformation-specific variant 2 (ETV2) and Slit3 induce Robo4 expression and activate Robo4 during tissue and organ development. Robo4 interacts with Slit2 or UNC5B to maintain vascular integrity, while a disturbed flow and the expression of transcription factors in inflammatory or neoplastic environments alter Robo4 expression levels, although these changes have uncertain functions. Based on the mechanisms described above, we discuss the aberrant expression of Robo4 in angiogenesis-related diseases and propose antiangiogenic therapies targeting the Robo4 signaling pathway for the treatment of ocular neovascularization lesions and tumors. Finally, although many problems related to Robo4 signaling pathways remain to be resolved, Robo4 is a promising and potentially valuable therapeutic target for treating pathological angiogenesis and developmental defects in angiogenesis.
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spelling pubmed-66203842019-07-24 Regulatory mechanisms of Robo4 and their effects on angiogenesis Dai, Chang Gong, Qiaoyun Cheng, Yan Su, Guanfang Biosci Rep Review Articles Roundabout4 (Robo4) is a transmembrane receptor that belongs to the Roundabout (Robo) family of axon guidance molecules. Robo4 is an endothelial-specific receptor that participates in endothelial cell migration, proliferation, and angiogenesis and the maintenance of vasculature homeostasis. The purpose of this review is to summarize and analyze three main mechanisms related to the expression and function of Robo4 during developmental and pathological angiogenesis. In this review, static shear stress and the binding of transcription factors such as E26 transformation-specific variant 2 (ETV2) and Slit3 induce Robo4 expression and activate Robo4 during tissue and organ development. Robo4 interacts with Slit2 or UNC5B to maintain vascular integrity, while a disturbed flow and the expression of transcription factors in inflammatory or neoplastic environments alter Robo4 expression levels, although these changes have uncertain functions. Based on the mechanisms described above, we discuss the aberrant expression of Robo4 in angiogenesis-related diseases and propose antiangiogenic therapies targeting the Robo4 signaling pathway for the treatment of ocular neovascularization lesions and tumors. Finally, although many problems related to Robo4 signaling pathways remain to be resolved, Robo4 is a promising and potentially valuable therapeutic target for treating pathological angiogenesis and developmental defects in angiogenesis. Portland Press Ltd. 2019-07-10 /pmc/articles/PMC6620384/ /pubmed/31160487 http://dx.doi.org/10.1042/BSR20190513 Text en © 2019 The Author(s). http://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Review Articles
Dai, Chang
Gong, Qiaoyun
Cheng, Yan
Su, Guanfang
Regulatory mechanisms of Robo4 and their effects on angiogenesis
title Regulatory mechanisms of Robo4 and their effects on angiogenesis
title_full Regulatory mechanisms of Robo4 and their effects on angiogenesis
title_fullStr Regulatory mechanisms of Robo4 and their effects on angiogenesis
title_full_unstemmed Regulatory mechanisms of Robo4 and their effects on angiogenesis
title_short Regulatory mechanisms of Robo4 and their effects on angiogenesis
title_sort regulatory mechanisms of robo4 and their effects on angiogenesis
topic Review Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6620384/
https://www.ncbi.nlm.nih.gov/pubmed/31160487
http://dx.doi.org/10.1042/BSR20190513
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