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- Title
Amino acid transporter SLC38A5 regulates developmental and pathological retinal angiogenesis.
- Authors
Zhongxiao Wang; Felix Yemanyi; Blomfield, Alexandra K.; Kiran Bora; Shuo Huang; Chi-Hsiu Liu; Britton, William R.; Steve S. Cho; Yohei Tomita; Zhongjie Fu; Jian-xing Ma; Wen-hong Li; Jing Chen
- Abstract
Amino acid (AA) metabolism in vascular endothelium is important for sprouting angiogenesis. SLC38A5 (solute carrier family 38 member 5), an AA transporter, shuttles neutral AAs across cell membrane, including glutamine, which may serve as metabolic fuel for proliferating endothelial cells (ECs) to promote angiogenesis. Here, we found that Slc38a5 is highly enriched in normal retinal vascular endothelium, and more specifically, in pathological sprouting neovessels. Slc38a5 is suppressed in retinal blood vessels from Lrp5-/- and Ndpy/- mice, both genetic models of defective retinal vascular development with Wnt signaling mutations. Additionally, Slc38a5 transcription is regulated by Wnt/β-catenin signaling. Genetic deficiency of Slc38a5 in mice substantially delays retinal vascular development and suppresses pathological neovascularization in oxygen-induced retinopathy modeling ischemic proliferative retinopathies. Inhibition of SLC38A5 in human retinal vascular ECs impairs EC proliferation and angiogenic function, suppresses glutamine uptake, and dampens vascular endothelial growth factor receptor 2. Together these findings suggest that SLC38A5 is a new metabolic regulator of retinal angiogenesis by controlling AA nutrient uptake and homeostasis in ECs.
- Subjects
RETROLENTAL fibroplasia; NEOVASCULARIZATION; VASCULAR endothelial growth factor receptors; AMINO acids; RETINAL blood vessels; HOMEOSTASIS; VASCULAR endothelium; WNT signal transduction
- Publication
eLife, 2022, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.73105