title: JAM-C maintains VEGR2 expression to promote retinal pigment epithelium cell survival under oxidative stress.
abstract: 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.
authors.forename: Xin
authors.initials: X
authors.lastname: Jia
authors.forename: Chen
authors.initials: C
authors.lastname: Zhao
authors.forename: Qishan
authors.initials: Q
authors.lastname: Chen
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Du
authors.forename: Lijuan
authors.initials: L
authors.lastname: Huang
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Ye
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Ren
authors.forename: Shasha
authors.initials: S
authors.lastname: Wang
authors.forename: Chunsik
authors.initials: C
authors.lastname: Lee
authors.forename: Zhongshu
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Xuri Li, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China, Tel.: +86 131 68358727, Fax: +86 020 87335176, E-mail: lixr6@mail.sysu.edu.cn.
authors.forename: Xuri
authors.initials: X
authors.lastname: Li
authors.affiliation: Rong Ju, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China, Tel.: +86 131 68358727, Fax: +86 020 87335176, E-mail: jurong@mail.sysu.edu.cn.
authors.forename: Rong
authors.initials: R
authors.lastname: Ju
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D034622:RNA Interference; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D014162:Transfection; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C448000:JAM3 protein, human; C486723:Jam3 protein, mouse; D006861:Hydrogen Peroxide; C000588866:KDR protein, human; C000592875:Kdr protein, mouse; D040301:Vascular Endothelial Growth Factor Receptor-2; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Junctional adhesion molecule-C; VEGR2; cell survival; retinal pigment epithelium cell