A CTGF-YAP Regulatory Pathway Is Essential for Angiogenesis and Barriergenesis in the Retina
Summary: 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...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-06-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004220303692 |
| _version_ | 1818434462049894400 |
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| author | Sohyun Moon Sangmi Lee Joy Ann Caesar Sarah Pruchenko Andrew Leask James A. Knowles Jose Sinon Brahim Chaqour |
| author_facet | Sohyun Moon Sangmi Lee Joy Ann Caesar Sarah Pruchenko Andrew Leask James A. Knowles Jose Sinon Brahim Chaqour |
| author_sort | Sohyun Moon |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-12-14T16:37:22Z |
| format | Article |
| id | doaj.art-0dd03b78704f430a8a85d4861f6ae3ca |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-14T16:37:22Z |
| publishDate | 2020-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-0dd03b78704f430a8a85d4861f6ae3ca2022-12-21T22:54:24ZengElsevieriScience2589-00422020-06-01236101184A CTGF-YAP Regulatory Pathway Is Essential for Angiogenesis and Barriergenesis in the RetinaSohyun Moon0Sangmi Lee1Joy Ann Caesar2Sarah Pruchenko3Andrew Leask4James A. Knowles5Jose Sinon6Brahim Chaqour7State University of New York, Downstate Health Science University, Department of Cell Biology, 450 Clarkson Avenue, MSC 5, Brooklyn, NY 11203, USAState University of New York, Downstate Health Science University, Department of Cell Biology, 450 Clarkson Avenue, MSC 5, Brooklyn, NY 11203, USAState University of New York, Downstate Health Science University, Department of Cell Biology, 450 Clarkson Avenue, MSC 5, Brooklyn, NY 11203, USAState University of New York, Downstate Health Science University, Department of Cell Biology, 450 Clarkson Avenue, MSC 5, Brooklyn, NY 11203, USAUniversity of Saskatchewan, College of Dentistry, E3338 HS - 105 Wiggins Road, Saskatoon, SK S7N 5E4, CanadaState University of New York, Downstate Health Science University, Department of Cell Biology, 450 Clarkson Avenue, MSC 5, Brooklyn, NY 11203, USAState University of New York, Downstate Health Science University, Department of Cell Biology, 450 Clarkson Avenue, MSC 5, Brooklyn, NY 11203, USAState University of New York, Downstate Health Science University, Department of Cell Biology, 450 Clarkson Avenue, MSC 5, Brooklyn, NY 11203, USA; State University of New York, Downstate Health Science University, Department of Ophthalmology, 450 Clarkson Avenue, Brooklyn, NY 11203, USA; SUNY Eye Institute, SUNY Downstate Health Science University, 450 Clarkson Avenue, Brooklyn, NY 11203, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004220303692Molecular BiologyCell BiologyTranscriptomics |
| spellingShingle | Sohyun Moon Sangmi Lee Joy Ann Caesar Sarah Pruchenko Andrew Leask James A. Knowles Jose Sinon Brahim Chaqour A CTGF-YAP Regulatory Pathway Is Essential for Angiogenesis and Barriergenesis in the Retina iScience Molecular Biology Cell Biology Transcriptomics |
| 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 | Molecular Biology Cell Biology Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004220303692 |
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