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FOXC1 regulates endothelial CD98 (LAT1/4F2hc) expression in retinal angiogenesis and blood-retina barrier formation

Author

Listed:
  • Teena Bhakuni

    (Northwestern University)

  • Pieter R. Norden

    (Northwestern University)

  • Naoto Ujiie

    (Northwestern University)

  • Can Tan

    (Northwestern University)

  • Sun Kyong Lee

    (Northwestern University)

  • Thomas Tedeschi

    (Northwestern University Feinberg School of Medicine)

  • Yi-Wen Hsieh

    (Northwestern University Feinberg School of Medicine)

  • Ying Wang

    (Mayo Clinic)

  • Ting Liu

    (Northwestern University)

  • Amani A. Fawzi

    (Northwestern University Feinberg School of Medicine)

  • Tsutomu Kume

    (Northwestern University)

Abstract

Angiogenesis, the growth of new blood vessels from pre-existing vasculature, is essential for the development of new organ systems, but transcriptional control of angiogenesis remains incompletely understood. Here we show that FOXC1 is essential for retinal angiogenesis. Endothelial cell (EC)-specific loss of Foxc1 impairs retinal vascular growth and expression of Slc3a2 and Slc7a5, which encode the heterodimeric CD98 (LAT1/4F2hc) amino acid transporter and regulate the intracellular transport of essential amino acids and activation of the mammalian target of rapamycin (mTOR). EC-Foxc1 deficiency diminishes mTOR activity, while administration of the mTOR agonist MHY-1485 rescues perturbed retinal angiogenesis. EC-Foxc1 expression is required for retinal revascularization and resolution of neovascular tufts in a model of oxygen-induced retinopathy. Foxc1 is also indispensable for pericytes, a critical component of the blood-retina barrier during retinal angiogenesis. Our findings establish FOXC1 as a crucial regulator of retinal vessels and identify therapeutic targets for treating retinal vascular disease.

Suggested Citation

  • Teena Bhakuni & Pieter R. Norden & Naoto Ujiie & Can Tan & Sun Kyong Lee & Thomas Tedeschi & Yi-Wen Hsieh & Ying Wang & Ting Liu & Amani A. Fawzi & Tsutomu Kume, 2024. "FOXC1 regulates endothelial CD98 (LAT1/4F2hc) expression in retinal angiogenesis and blood-retina barrier formation," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48134-2
    DOI: 10.1038/s41467-024-48134-2
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