title: Regulation of endothelial progenitor cell release by Wnt signaling in bone marrow.
abstract: OBJECTIVE
  Endothelial progenitor cells (EPC) have been shown to participate in ischemia-induced retinal neovascularization (NV). Overactivation of Wnt signaling has a pathogenic role in ischemia-induced retinal NV. The purpose of this study is to determine whether Wnt signaling regulates EPC release.
  
  
  METHODS
  Oxygen-induced retinopathy (OIR) was used as a model of retinal NV and Wnt pathway activation. The EPC, marked as c-Kit(+)/Tie-2(+) cells in the peripheral blood and bone marrow, were quantified using flow cytometry following immunolabeling. The Wnt signaling activity was evaluated by measuring nonphosphorylated β-catenin levels and X-gal staining in the Wnt reporter mice (Bat-gal mice).
  
  
  RESULTS
  The c-Kit(+)/Tie-2(+) cells were increased significantly in the peripheral blood and bone marrow of mice with OIR, compared to non-OIR mice. Overexpression of kallistatin, an endogenous inhibitor of the Wnt pathway, in kallistatin transgenic (kallistatin-TG) mice with OIR attenuated the increases of c-Kit(+)/Tie-2(+) cells in the peripheral blood and bone marrow, compared to WT mice with OIR. When the Bat-gal mice were crossed with kallistatin-TG mice, kallistatin overexpression suppressed the OIR-induced increases of X-gal-positive cells in the retinas and bone marrow, suggesting inhibition of Wnt signaling in these tissues. Furthermore, intraperitoneal injection of LiCl, a Wnt signaling activator, increased c-Kit(+)/Tie-2(+) cells in the peripheral blood of normal mice. Consistently, LiCl activated Wnt signaling in the retina and bone marrow cells in Bat-gal mice.
  
  
  CONCLUSIONS
  The Wnt signaling pathway has an important role in EPC release during retinal NV in OIR.
authors.affiliation: Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, China.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Liu
authors.forename: Jeffrey
authors.initials: J
authors.lastname: McBride
authors.forename: Yueping
authors.initials: Y
authors.lastname: Zhou
authors.forename: Zuguo
authors.initials: Z
authors.lastname: Liu
authors.forename: Jian-Xing
authors.initials: JX
authors.lastname: Ma
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D042787:Receptor, TIE-2 / Q000378:metabolism; D015861:Retinal Neovascularization / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000502:physiology*
chemical_list: D019009:Proto-Oncogene Proteins c-kit; D042787:Receptor, TIE-2; C079086:Tek protein, mouse
keywords: EPC; Wnt; bone marrow; peripheral blood; retina