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Novel Regulators of Retina Neovascularization: A Proteomics Approach.

Abstract
The purpose of this study was to identify proteins that regulate vascular remodeling in an ROP mouse model. Pups were subjected to fluctuating oxygen levels and retinas sampled during vessel regression (PN12) or neovascularization (PN17) for comparative SWATH-MS proteomics using liquid chromatography-tandem mass spectrometry (LC-MS/MS). We developed a human retinal endothelial cell (HREC) ROP correlate to validate the expression of retina neovascular-specific markers. A total of 5191 proteins were identified in OIR retinas with 498 significantly regulated in elevated oxygen and 345 after a return to normoxia. A total of 122 proteins were uniquely regulated during vessel regression and 69 during neovascularization (FC ≥ 1.5; p ≤ 0.05), with several validated by western blot analyses. Expressions of 56/69 neovascular-specific proteins were confirmed in hypoxic HRECs with 23 regulated in the same direction as OIR neovascular retinas. These proteins control angiogenesis-related processes including matrix remodeling, cell migration, adhesion, and proliferation. RNAi and transfection overexpression studies confirmed that VASP and ECH1, showing the highest levels in hypoxic HRECs, promoted human umbilical vein (HUVEC) and HREC cell proliferation, while SNX1 and CD109, showing the lowest levels, inhibited their proliferation. These proteins are potential biomarkers and exploitable intervention tools for vascular-related disorders. The proteomics data set generated has been deposited to the ProteomeXchange/iProX Consortium with the Identifier:PXD029208.
AuthorsManhong Xu, Yilin Jiang, Lin Su, Xin Chen, Xianfeng Shao, Vicki Ea, Zhenying Shang, Xiaomin Zhang, Colin J Barnstable, Xiaorong Li, Joyce Tombran-Tink
JournalJournal of proteome research (J Proteome Res) Vol. 21 Issue 1 Pg. 101-117 (01 07 2022) ISSN: 1535-3907 [Electronic] United States
PMID34919406 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Vascular Endothelial Growth Factor A
  • Oxygen
Topics
  • Animals
  • Animals, Newborn
  • Chromatography, Liquid
  • Disease Models, Animal
  • Humans
  • Infant, Newborn
  • Mice
  • Mice, Inbred C57BL
  • Oxygen (metabolism)
  • Proteomics
  • Retina
  • Retinopathy of Prematurity (metabolism)
  • Tandem Mass Spectrometry
  • Vascular Endothelial Growth Factor A (metabolism)

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