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Int J Biol Sci 2019; 15(3):507-521. doi:10.7150/ijbs.30575

Research Paper

Autophagy resists EMT process to maintain retinal pigment epithelium homeostasis

Hao Feng1,2, Xin Zhao2, Qiqiang Guo2, Yanling Feng2, Mengtao Ma2, Wendong Guo2, Xiang Dong2, Chengsi Deng2, Chunlu Li2, Xiaoyu Song2, Shuai Han3✉, Liu Cao2✉

1. Department of Ophthalmology, The First Hospital of China Medical University, Shenyang, Liaoning Province, 110122, China
2. Key Laboratory of Medical Cell Biology, Ministry of Education; Institute of Translational Medicine, China Medical University; Liaoning Province, Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, Shenyang, Liaoning Province, 110122, China
3. Department of Neurosurgery, The First Hospital of China medical University, Shenyang, Liaoning Province, 110122, China

Abstract

Proliferative vitreoretinopathy (PVR) is the most serious fibrous complication that causes vision loss after intraocular surgery, and there is currently no effective treatment in clinical. Autophagy is an important cell biological mechanism in maintaining the homeostasis of tissues and cells, resisting the process of EMT. However, it is still unclear whether autophagy could resist intraocular fibrosis and prevent PVR progression. In this study, we investigated the expression of mesenchymal biomarkers in autophagy deficiency cells and found these proteins were increased. The mesenchymal protein transcription factor Twist can bind to autophagy related protein p62 and promote the degradation of Twist, which reduced the expression of mesenchymal markers. By constructing an EMT model of retinal pigment epithelial (RPE) cells in vitro, we found that autophagy was activated in the EMT process of RPE cells. Moreover, in autophagy deficient RPE cell line via knockdown autophagy related protein 7 (Atg7), the expression of epithelial marker claudin-1 was suppressed and the mesenchymal markers were increased, accompanied by an increase in cell migration and contractility. Importantly, RPE epithelial properties can be maintained by promoting autophagy and effectively reversing TFG-β2-induced RPE fibrosis. These observations reveal that autophagy may be an effective way to treat PVR.

Keywords: Autophagy, Proliferative vitreoretinopathy, Retinal pigment epithelial, EMT, Atg7, Twist

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Feng H, Zhao X, Guo Q, Feng Y, Ma M, Guo W, Dong X, Deng C, Li C, Song X, Han S, Cao L. Autophagy resists EMT process to maintain retinal pigment epithelium homeostasis. Int J Biol Sci 2019; 15(3):507-521. doi:10.7150/ijbs.30575. Available from http://www.ijbs.com/v15p0507.htm