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.
引用
收藏
页码:7386 / 7394
页数:9
相关论文
共 31 条
[1]   Circulating bone-marrow-derived endothelial precursor cells contribute to neovascularization in diabetic epiretinal membranes [J].
Abu El-Asrar, Ahmed M. ;
Struyf, Sofie ;
Verbeke, Hannelien ;
Van Damme, Jo ;
Geboes, Karel .
ACTA OPHTHALMOLOGICA, 2011, 89 (03) :222-228
[2]   Increase of circulating endothelial progenitor cells in patients with coronary artery disease after exercise-induced ischemia [J].
Adams, V ;
Lenk, K ;
Linke, A ;
Lenz, D ;
Erbs, S ;
Sandri, M ;
Tarnok, A ;
Gielen, S ;
Emmrich, F ;
Schuler, G ;
Hambrecht, R .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2004, 24 (04) :684-690
[3]   Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization [J].
Asahara, T ;
Masuda, H ;
Takahashi, T ;
Kalka, C ;
Pastore, C ;
Silver, M ;
Kearne, M ;
Magner, M ;
Isner, JM .
CIRCULATION RESEARCH, 1999, 85 (03) :221-228
[4]   TGF-β and BMP Signaling in Osteoblast Differentiation and Bone Formation [J].
Chen, Guiqian ;
Deng, Chuxia ;
Li, Yi-Ping .
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES, 2012, 8 (02) :272-288
[5]   Activation of the Wnt Pathway Plays a Pathogenic Role in Diabetic Retinopathy in Humans and Animal Models [J].
Chen, Ying ;
Hu, Yang ;
Zhou, Ti ;
Zhou, Kevin K. ;
Mott, Robert ;
Wu, Mingyuan ;
Boulton, Michael ;
Lyons, Timothy J. ;
Gao, Guoquan ;
Ma, Jian-xing .
AMERICAN JOURNAL OF PATHOLOGY, 2009, 175 (06) :2676-2685
[6]   Bone marrow-derived progenitor cells contribute to experimental choroidal neovascularization [J].
Espinosa-Heidmann, DG ;
Caicedo, A ;
Hernandez, EP ;
Csaky, KG ;
Cousins, SW .
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2003, 44 (11) :4914-4919
[7]   Unbalanced expression of VEGF and PEDF in ischemia-induced retinal neovascularization [J].
Gao, GQ ;
Li, Y ;
Zhang, DC ;
Gee, S ;
Crosson, C ;
Ma, JX .
FEBS LETTERS, 2001, 489 (2-3) :270-276
[8]   Wnt pathway - A new role in regulation of inflammation [J].
George, Sarah Jane .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2008, 28 (03) :400-402
[9]   Circulating endothelial progenitor cells, vascular function, and cardiovascular risk [J].
Hill, JM ;
Zalos, G ;
Halcox, JPJ ;
Schenke, WH ;
Waclawiw, MA ;
Quyyumi, AA ;
Finkel, T .
NEW ENGLAND JOURNAL OF MEDICINE, 2003, 348 (07) :593-600
[10]   Assessing identity, phenotype, and fate of endothelial progenitor cells [J].
Hirschi, Karen K. ;
Ingram, David A. ;
Yoder, Mervin C. .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2008, 28 (09) :1584-1595