JAM-C maintains VEGR2 expression to promote retinal pigment epithelium cell survival under oxidative stress
Autor: | Qishan Chen, Xiangrong Ren, Xin Jia, Xuri Li, Chunsik Lee, Yuxiang Du, Chen Zhao, Lijuan Huang, Zhimin Ye, Shasha Wang, Rong Ju, Zhongshu Tang |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Cell Survival p38 mitogen-activated protein kinases Immunoglobulins Retinal Pigment Epithelium Biology medicine.disease_cause Transfection p38 Mitogen-Activated Protein Kinases Cell Line 03 medical and health sciences Immune system medicine Animals Humans Phosphorylation Gene knockdown Retinal pigment epithelium fungi Epithelial Cells Hematology Hydrogen Peroxide Vascular Endothelial Growth Factor Receptor-2 humanities eye diseases In vitro Cell biology Mice Inbred C57BL Oxidative Stress 030104 developmental biology medicine.anatomical_structure cardiovascular system Female RNA Interference sense organs Junctional Adhesion Molecule C Cell Adhesion Molecules Oxidative stress Signal Transduction |
Zdroj: | Thrombosis and haemostasis. 117(4) |
ISSN: | 2567-689X |
Popis: | SummaryJunctional 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. |
Databáze: | OpenAIRE |
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