Chang Kyung-Hee, Chan-Ling Tailoi, McFarland Evan L, Afzal Aqeela, Pan Hao, Baxter Louise C, Shaw Lynn C, Caballero Sergio, Sengupta Nilanjana, Li Calzi Sergio, Sullivan Sean M, Grant Maria B
Program in Stem Cell Biology, University of Florida, Gainesville, FL 32610, USA.
Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10595-600. doi: 10.1073/pnas.0702072104. Epub 2007 Jun 13.
We asked whether the hypoxia-regulated factor, insulin-like growth factor binding protein-3 (IGFBP3), could modulate stem cell factor receptor (c-kit+), stem cell antigen-1 (sca-1+), hematopoietic stem cell (HSC), or CD34+ endothelial precursor cell (EPC) function. Exposure of CD34+ EPCs to IGFBP3 resulted in rapid differentiation into endothelial cells and dose-dependent increases in cell migration and capillary tube formation. IGFBP3-expressing plasmid was injected into the vitreous of neonatal mice undergoing the oxygen-induced retinopathy (OIR) model. In separate studies, GFP-expressing HSCs were transfected with IGFBP3 plasmid and injected into the vitreous of OIR mice. Administering either IGFBP3 plasmid alone or HSCs transfected with the plasmid resulted in a similar reduction in areas of vasoobliteration, protection of the developing vasculature from hyperoxia-induced regression, and reduction in preretinal neovascularization compared to control plasmid or HSCs transfected with control plasmid. In conclusion, IGFBP3 mediates EPC migration, differentiation, and capillary formation in vitro. Targeted expression of IGFBP3 protects the vasculature from damage and promotes proper vascular repair after hyperoxic insult in the OIR model. IGFBP3 expression may represent a physiological adaptation to ischemia and potentially a therapeutic target for treatment of ischemic conditions.
我们探究了缺氧调节因子胰岛素样生长因子结合蛋白3（IGFBP3）是否能够调节干细胞因子受体（c-kit+）、干细胞抗原1（sca-1+）、造血干细胞（HSC）或CD34+内皮祖细胞（EPC）的功能。将CD34+ EPC暴露于IGFBP3会导致其迅速分化为内皮细胞，并使细胞迁移和毛细血管管腔形成呈剂量依赖性增加。将表达IGFBP3的质粒注射到处于氧诱导视网膜病变（OIR）模型的新生小鼠玻璃体内。在另外的研究中，将表达绿色荧光蛋白（GFP）的HSCs用IGFBP3质粒转染后注射到OIR小鼠的玻璃体内。单独给予IGFBP3质粒或用该质粒转染的HSCs，与对照质粒或用对照质粒转染的HSCs相比，均能使血管闭塞面积有类似程度的减小，保护发育中的脉管系统免受高氧诱导的退化，并减少视网膜前新生血管形成。总之，IGFBP3在体外介导EPC的迁移、分化和毛细血管形成。在OIR模型中，靶向表达IGFBP3可保护脉管系统免受损伤，并促进高氧损伤后血管的正常修复。IGFBP3的表达可能代表了对缺血的一种生理适应，并且可能是治疗缺血性疾病的一个治疗靶点。
