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Liu Lixian, Rongyuan Chen, Chunsik Lee, Xuri Li; Mig6 exhibits anti-angiogenic effect by modulate endothelial cell proliferation and apoptosis. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5485.
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© ARVO (1962-2015); The Authors (2016-present)
Pathologic ocular neovascularization is one of the causes of blindness. Mitogen-Inducible Gene 6 (Mig6), a negative feedback of epithelial growth factor receptor (EGFR) signaling, is regarded as tumor suppressor that inhibits cancer cell proliferation and promotes apoptosis. However, it is unknown whether Mig6 involves in the ocular neovascularization. The current study aims to investigate the potential role of Mig6 in regulating ocular neovascularization by hypothesizing that Mig6 has anti-angiogenic effect via modulating endothelial cell proliferation and apoptosis.
Loss-of-function and gain-of-function studies were performed in human retinal microvascular endothelial cells (HREC) and in choroid explants from C57BL/6N mice.We first examined mRNA and protein level of Mig6 under stimulation with EGF in HREC. MTT assay and wound healing assay were carried out to check the EC functions. Cleaved caspase 3 protein level examination and TUNEL assay were used to detect apoptosis. To investigate the effects of Mig6 on angiogenesis in ex vivo tissue explants, choroid sprouting assay was done. Key molecules of both proliferative and apoptotic pathways were detected by western blot. Two-tailed Student's t-test was used for statistical analysis.
Mig6 expression in HREC was up-regulated in response to EGF in both mRNA and protein level. Knockdown of Mig6 resulted in increase of the capacity of proliferation and migration. Significantly lower levels of apoptosis were detected in Mig6 deficient HREC, which was consistent with decreases in cleaved caspase 3 protein . In the choroid sprouting assay, Mig6 overexpressing choroid explants showed reduction of outgrowth. Silencing endogenous Mig6 enhanced EGF-induced activation of ERK, and AKT, as well as Bad phosphorylation. These data demonstrate that Mig6 exerts anti-angiogenic effects on endothelial cell by modulating cell proliferation and apoptosis.
This study provides the first evidence that Mig6 exerts anti-angiogenic effects in endothelial cell by modulating cell proliferation and apoptosis.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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