Amino acid transporter SLC38A5 regulates developmental and pathological retinal angiogenesis

Zhongxiao Wang, Felix Yemanyi, Alexandra K. Blomfield, Kiran Bora, Shuo Huang, Chi Hsiu Liu, William R. Britton, Steve S. Cho, Yohei Tomita, Zhongjie Fu, Jian Xing Ma, Wen Hong Li, Jing Chen

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Amino acid (AA) metabolism in vascular endothelium is important for sprouting angio-genesis. 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 defec-tive 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.

Original languageEnglish
Article numbere73105
JournaleLife
Volume11
DOIs
Publication statusPublished - 2022
Externally publishedYes

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry,Genetics and Molecular Biology
  • General Immunology and Microbiology

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