Annexin A2 upregulation protects human retinal endothelial cells from oxygen‑glucose deprivation injury by activating autophagy

Jiang,Shule; Xu,Yile

doi:10.3892/etm.2019.7909

Annexin A2 upregulation protects human retinal endothelial cells from oxygen‑glucose deprivation injury by activating autophagy

Authors:
- Shule Jiang
- Yile Xu
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Affiliations: Department of Ophthalmology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China, Department of Ophthalmology, The Hangzhou First People's Hospital, Hangzhou, Zhejiang 310001, P.R. China
Published online on: August 16, 2019 https://doi.org/10.3892/etm.2019.7909
Pages: 2901-2908
Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Retinal neovascularization is a common pathological change in multiple diseases of the eyes and the upregulation of annexin A2 (A2) under a hypoxic and ischemic microenvironment has been demonstrated to be a key factor in the pathological process. However, the underlying mechanism by which A2 regulates retinal neovascularization remains unclear. In the present study, oxygen‑glucose deprivation (OGD) was used to mimic the hypoxic and ischemic microenvironment, to observe the role of A2 in retinal neovascularization regulation by focusing on autophagy. The results showed that OGD treatment significantly increased the mRNA and protein levels of A2 in human retinal endothelial cells (HRECs), which was dependent on activation of hypoxia inducible factor (HIF)‑1α signaling. The OGD‑induced activation of autophagy was attenuated when A2 was silenced, but increased when A2 was overexpressed, suggesting that A2 upregulation contributed to OGD‑induced cell autophagy activation. Furthermore, knockdown of A2 decreased cell viability and promoted cell apoptosis under OGD conditions. Overexpression of A2 increased cell viability and reduced cell apoptosis under OGD conditions, and inhibiting autophagy using an inhibitor, reversed these changes, suggesting that upregulation of A2 by OGD serves a cytoprotective role by inducing cell autophagy in HRECs. Taken together, the results of the present study suggested that promoting retinal endothelial cell survival by autophagy activation via the HIF‑1α signaling pathway in a hypoxic and ischemic microenvironment may underlie the mechanism by which A2 regulates retinal neovascularization. The present study is the first study to demonstrate the novel role of A2 during retinal neovascularization under pathological conditions, to the best of our knowledge. Therefore, A2 may serve as a potential therapeutic target for treating neovascularization‑associated conditions of the eye.

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