IGF binding protein-3 regulates hematopoietic stem cell and endothelial precursor cell function during vascular development.

作者: K.-H. Chang , T. Chan-Ling , E. L. McFarland , A. Afzal , H. Pan

DOI: 10.1073/PNAS.0702072104

关键词: AngiogenesisNeovascularizationGrowth factorHematopoietic stem cellCancer researchBiologyStem cellStem cell factorCD34Proto-Oncogene Proteins c-kit

摘要: We asked whether the hypoxia-regulated factor, insulin-like growth factor binding protein-3 (IGFBP3), could modulate stem cell receptor (c-kit+), antigen-1 (sca-1+), hematopoietic (HSC), or CD34+ endothelial precursor (EPC) function. Exposure of EPCs to IGFBP3 resulted in rapid differentiation into cells and dose-dependent increases migration capillary tube formation. IGFBP3-expressing plasmid was injected vitreous neonatal mice undergoing oxygen-induced retinopathy (OIR) model. In separate studies, GFP-expressing HSCs were transfected with OIR mice. Administering either alone a similar reduction areas vasoobliteration, protection developing vasculature from hyperoxia-induced regression, preretinal neovascularization compared control plasmid. conclusion, mediates EPC migration, differentiation, formation vitro. Targeted expression protects damage promotes proper vascular repair after hyperoxic insult may represent physiological adaptation ischemia potentially therapeutic target for treatment ischemic conditions.

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