共 31 条
Regulation of Endothelial Progenitor Cell Release by Wnt Signaling in Bone Marrow
被引:11
作者:
Liu, Xiaochen
[1
,2
]
McBride, Jeffrey
[3
]
Zhou, Yueping
[1
]
Liu, Zuguo
[1
]
Ma, Jian-xing
[2
]
机构:
[1] Xiamen Univ, Fujian Prov Key Lab Ophthalmol & Visual Sci, Eye Inst, Xiamen, Peoples R China
[2] Univ Oklahoma, Hlth Sci Ctr, Dept Physiol, Oklahoma City, OK USA
[3] Univ Oklahoma, Hlth Sci Ctr, Dept Cell Biol, Oklahoma City, OK USA
基金:
美国国家卫生研究院;
关键词:
EPC;
bone marrow;
peripheral blood;
retina;
Wnt;
DIABETIC-RETINOPATHY;
GROWTH-FACTOR;
NEOVASCULARIZATION;
PATHWAY;
ISCHEMIA;
DIFFERENTIATION;
HEMATOPOIESIS;
MOBILIZATION;
EXPRESSION;
CONTRIBUTE;
D O I:
10.1167/iovs.13-13163
中图分类号:
R77 [眼科学];
学科分类号:
100212 ;
摘要:
PURPOSE. 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 beta-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.
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页码:7386 / 7394
页数:9
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