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Xiu-Mei Yang, Chun-Guang Duan, Jian Zhang, Xiao-Jie Qu, Yu-Sheng Wang; Integrin-Linked Kinase Controls Choroidal Neovascularization by Recruitment of Endothelial Progenitor Cells. Invest. Ophthalmol. Vis. Sci. 2018;59(5):1779-1789. doi: 10.1167/iovs.17-22931.
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Vasculogenesis has been shown to contribute to the formation of choroidal neovascularization (CNV). However, the mechanism behind the recruitment of endothelial progenitor cells (EPC) to CNV is not well understood. Therefore, we were interested to know whether integrin-linked kinase (ILK) plays a role in recruiting EPC to CNV, and its possible mechanism.
We investigated the effect of hypoxia on retinal pigment epithelium (RPE) cells expressing ILK, hypoxia-inducible factor 1α (HIF-1α), stromal-derived factor-1 (SDF-1), and vascular endothelial growth factor (VEGF), and we further examined the effect of ILK small interfering RNA (siRNA) on their expression. The function of ILK expressed by RPE on EPC in vitro with regard to angiogenic effect was also studied. In vivo, we determined the expression levels of the above factors in CNV. We also examined the role of ILK on their expression, on EPC recruiting, and on the growth of CNV.
We found that hypoxia strongly induced the expression of ILK, HIF-1α, SDF-1, and VEGF. Moreover, the silencing of ILK attenuated their expression. It also decreased the phosphorylation of protein kinase B (PKB/AKT) and extracellular regulated protein kinases (ERK) and nearly abolished the proliferation, migration, and adhesion of EPC to RPE cells. In vivo, we showed that these factors were upregulated in CNV. Inhibiting the expression of ILK prohibited the “homing” of EPC to CNV lesions and attenuated the growth of CNV.
We demonstrate that ILK controls the development of CNV by regulating the recruitment of EPC to CNV lesions, possibly through ILK-dependent expression of SDF-1 and VEGF in RPE.
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