iScience
Volume 23, Issue 6, 26 June 2020, 101184
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Article
A CTGF-YAP Regulatory Pathway Is Essential for Angiogenesis and Barriergenesis in the Retina

https://doi.org/10.1016/j.isci.2020.101184Get rights and content
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Highlights

  • CTGF has a strong and persistent expression in the retinal vasculature

  • Mice lacking CTGF exhibit defects in angiogenesis and blood barrier integrity

  • CTGF-targeted genes include matrix, growth, and transcription co-factors like YAP

  • YAP re-expression partly rescues angiogenic and barriergenic defects of CTGF loss

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.

Subject Areas

Molecular Biology
Cell Biology
Transcriptomics

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