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A CTGF-YAP Regulatory Pathway Is Essential for Angiogenesis and Barriergenesis in the Retina

Connective tissue growth factor (CTGF) or cellular communication network 2 (CCN2) is a matricellular protein essential for normal embryonic development and tissue repair. CTGF exhibits cell- and context-dependent activities, but CTGF function in vascular development and barrier function is unknown....

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Autores principales: Moon, Sohyun, Lee, Sangmi, Caesar, Joy Ann, Pruchenko, Sarah, Leask, Andrew, Knowles, James A., Sinon, Jose, Chaqour, Brahim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270711/
https://www.ncbi.nlm.nih.gov/pubmed/32502964
http://dx.doi.org/10.1016/j.isci.2020.101184
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author Moon, Sohyun
Lee, Sangmi
Caesar, Joy Ann
Pruchenko, Sarah
Leask, Andrew
Knowles, James A.
Sinon, Jose
Chaqour, Brahim
author_facet Moon, Sohyun
Lee, Sangmi
Caesar, Joy Ann
Pruchenko, Sarah
Leask, Andrew
Knowles, James A.
Sinon, Jose
Chaqour, Brahim
author_sort Moon, Sohyun
collection PubMed
description Connective tissue growth factor (CTGF) or cellular communication network 2 (CCN2) is a matricellular protein essential for normal embryonic development and tissue repair. CTGF exhibits cell- and context-dependent activities, but CTGF function in vascular development and barrier function is unknown. We show that endothelial cells (ECs) are one of the major cellular sources of CTGF in the developing and adult retinal vasculature. Mice lacking CTGF expression either globally or specifically in ECs exhibit impaired vascular cell growth and morphogenesis and blood barrier breakdown. The global molecular signature of CTGF includes cytoskeletal and extracellular matrix protein, growth factor, and transcriptional co-regulator genes such as yes-associated protein (YAP). YAP, itself a transcriptional activator of CTGF, mediates several CTGF-controlled angiogenic and barriergenic transcriptional programs. Re-expression of YAP rescues, at least partially, angiogenesis and barriergenesis in CTGF mutant mouse retinas. Thus, the CTGF-YAP regulatory loop is integral to retinal vascular development and barrier function.
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spelling pubmed-72707112020-06-08 A CTGF-YAP Regulatory Pathway Is Essential for Angiogenesis and Barriergenesis in the Retina Moon, Sohyun Lee, Sangmi Caesar, Joy Ann Pruchenko, Sarah Leask, Andrew Knowles, James A. Sinon, Jose Chaqour, Brahim iScience Article Connective tissue growth factor (CTGF) or cellular communication network 2 (CCN2) is a matricellular protein essential for normal embryonic development and tissue repair. CTGF exhibits cell- and context-dependent activities, but CTGF function in vascular development and barrier function is unknown. We show that endothelial cells (ECs) are one of the major cellular sources of CTGF in the developing and adult retinal vasculature. Mice lacking CTGF expression either globally or specifically in ECs exhibit impaired vascular cell growth and morphogenesis and blood barrier breakdown. The global molecular signature of CTGF includes cytoskeletal and extracellular matrix protein, growth factor, and transcriptional co-regulator genes such as yes-associated protein (YAP). YAP, itself a transcriptional activator of CTGF, mediates several CTGF-controlled angiogenic and barriergenic transcriptional programs. Re-expression of YAP rescues, at least partially, angiogenesis and barriergenesis in CTGF mutant mouse retinas. Thus, the CTGF-YAP regulatory loop is integral to retinal vascular development and barrier function. Elsevier 2020-05-21 /pmc/articles/PMC7270711/ /pubmed/32502964 http://dx.doi.org/10.1016/j.isci.2020.101184 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Moon, Sohyun
Lee, Sangmi
Caesar, Joy Ann
Pruchenko, Sarah
Leask, Andrew
Knowles, James A.
Sinon, Jose
Chaqour, Brahim
A CTGF-YAP Regulatory Pathway Is Essential for Angiogenesis and Barriergenesis in the Retina
title A CTGF-YAP Regulatory Pathway Is Essential for Angiogenesis and Barriergenesis in the Retina
title_full A CTGF-YAP Regulatory Pathway Is Essential for Angiogenesis and Barriergenesis in the Retina
title_fullStr A CTGF-YAP Regulatory Pathway Is Essential for Angiogenesis and Barriergenesis in the Retina
title_full_unstemmed A CTGF-YAP Regulatory Pathway Is Essential for Angiogenesis and Barriergenesis in the Retina
title_short A CTGF-YAP Regulatory Pathway Is Essential for Angiogenesis and Barriergenesis in the Retina
title_sort ctgf-yap regulatory pathway is essential for angiogenesis and barriergenesis in the retina
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270711/
https://www.ncbi.nlm.nih.gov/pubmed/32502964
http://dx.doi.org/10.1016/j.isci.2020.101184
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