華盛頓大學(xué)醫(yī)學(xué)院的發(fā)育生物學(xué)教授David M. Ornitz博士，研究了一組稱為成纖維細胞生長因子(或FGF蛋白家族)的蛋白質(zhì)。FGF蛋白質(zhì)是在胚胎發(fā)育、組織維護和傷口愈合中發(fā)揮廣泛作用的信號分子。它們與特定受體分子FGFRs(位于身體許多類型細胞的表面)相互作用。
Endothelial cell FGF signaling is required for injury response but not for vascularhomeostasis
Sunday S. Oladipupo, Craig Smith, Andrea Santeford, Changwon Park, Abdoulaye Sene,Luke A. Wiley, Patrick Osei-Owusu, Joann Hsu, Nicole Zapata, Fang Liu, Rei Nakamura,Kory J. Lavine, Kendall J. Blumer, Kyunghee Choi, Rajendra S. Apte, and David M. Ornitz
Endothelial cells (ECs) express fibroblast growth factor receptors (FGFRs) and are exquisitely sensitive to FGF signals. However, whether the EC or another vascular cell type requiresFGF signaling during development, homeostasis, and responseto injury is not known. Here, we show that Flk1-Cre or Tie2-Cre mediated deletion of FGFR1 and FGFR2 (Fgfr1/2Flk1-Creor Fgfr1/2Tie2-Cre mice), which results in deletion inendothelial and hematopoietic cells, is compatible with normal embryonic development. As adults, Fgfr1/2Flk1-Cre mice maintain normal blood pressure and vascular reactivity and integrity under homeostatic conditions. However, neovascularization after skin or eye injury was significantly impaired in both Fgfr1/2Flk1-Cre and Fgfr1/2Tie2-Cre mice, independent of either hematopoietic cell loss of FGFR1/2 orvascular endothelial growth factor receptor 2 (Vegfr2) haploinsufficiency. Also, impaired neovascularization was associated with delayed cutaneous wound healing. These findings reveal a key requirement for cell-autonomous ECFGFR signaling in injury-induced angiogenesis, but not forvascular homeostasis, identifying the EC FGFR signalingpathway as a target for diseases associated with aberrantvascular proliferation, such as age-related macular degeneration, and for modulating wound healing without the potential toxicity associated with direct manipulation of systemic FGF or VEGF activity.
