Purchase this article with an account.
Xiaochen Liu, Jeffrey McBride, Yueping Zhou, Zuguo Liu, Jian-xing Ma; Regulation of Endothelial Progenitor Cell Release by Wnt Signaling in Bone Marrow. Invest. Ophthalmol. Vis. Sci. 2013;54(12):7386-7394. doi: 10.1167/iovs.13-13163.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
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.
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).
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.
The Wnt signaling pathway has an important role in EPC release during retinal NV in OIR.
This PDF is available to Subscribers Only