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Thromb Haemost 2017; 117(04): 750-757
DOI: 10.1160/TH16-11-0885
Endothelium and Angiogenesis
Schattauer GmbH

JAM-C maintains VEGR2 expression to promote retinal pigment epithelium cell survival under oxidative stress

Xin Jia   #
1   State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, P. R. China
,
Chen Zhao   #
2   Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, P. R. China
,
Qishan Chen
1   State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, P. R. China
,
Yuxiang Du
1   State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, P. R. China
,
Lijuan Huang
1   State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, P. R. China
,
Zhimin Ye
1   State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, P. R. China
,
Xiangrong Ren
1   State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, P. R. China
,
Shasha Wang
1   State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, P. R. China
,
Chunsik Lee
1   State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, P. R. China
,
Zhongshu Tang
1   State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, P. R. China
,
Xuri Li
1   State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, P. R. China
,
Rong Ju
2   Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, P. R. China
› Author Affiliations Financial support: This research was supported by a grant of the National Natural Science Foundation of China to R. Ju. (81470644); the State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University in Guangzhou; an Innovation Team Program of the Jiangsu Province to C. Zhao and X. Li; a key program of the National Natural Science Foundation of China (81330021) to X. Li .
Further Information

Publication History

Received: 25 November 2016

Accepted after minor revision: 23 January 2017

Publication Date:
28 November 2017 (online)

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Summary

Junctional adhesion molecule-C (JAM-C) has been shown to play critical roles during development and in immune responses. However, its role in adult eyes under oxidative stress remains poorly understood. Here, we report that JAM-C is abundantly expressed in adult mouse retinae and choroids in vivo and in cultured retinal pigment epithelium (RPE) and photoreceptor cells in vitro. Importantly, both JAM-C expression and its membrane localisation are downregulated by H2O2-induced oxidative stress. Under H2O2-induced oxidative stress, JAM-C is critically required for the survival of human RPE cells. Indeed, loss of JAM-C by siRNA knockdown decreased RPE cell survival. Mechanistically, we show that JAM-C is required to maintain VEGFR2 expression in RPE cells, and VEGFR2 plays an important role in keeping the RPE cells viable since overexpression of VEGFR2 partially restored impaired RPE survival caused by JAM-C knockdown and increased RPE survival. We further show that JAM-C regulates VEGFR2 expression and, in turn, modulates p38 phosphorylation. Together, our data demonstrate that JAM-C plays an important role in maintaining VEGR2 expression to promote RPE cell survival under oxidative stress. Given the vital importance of RPE in the eye, approaches that can modulate JAM-C expression may have therapeutic values in treating diseases with impaired RPE survival.

Keywords

Junctional adhesion molecule-C - VEGR2 - retinal pigment epithelium cell - cell survival

# Equal first authors.


 

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