Role of Junctional Adhesion Molecule-C in the Regulation of Inner Endothelial Blood-Retinal Barrier Function

被引:7
|
作者
Hou, Xu [1 ]
Du, Hong-Jun [1 ]
Zhou, Jian [1 ]
Hu, Dan [1 ]
Wang, Yu-Sheng [1 ]
Li, Xuri [2 ]
机构
[1] Fourth Mil Med Univ, Dept Ophthalmol, Eye Inst Chinese PLA, Xijing Hosp, Xian, Peoples R China
[2] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou, Peoples R China
基金
中国国家自然科学基金;
关键词
junctional adhesion molecule-C; blood-retinal barrier; retinal capillary endothelial cell; vascular endothelial growth factor; platelet-derived growth factor-C; PROTEIN-KINASE-C; TRANSENDOTHELIAL MIGRATION; JAM-C; EXPRESSION; CELLS; CALCIUM; IDENTIFICATION; ANGIOGENESIS; PERMEABILITY; CHANNELS;
D O I
10.3389/fcell.2021.695657
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Although JAM-C is abundantly expressed in the retinae and upregulated in choroidal neovascularization (CNV), it remains thus far poorly understood whether it plays a role in the blood-retinal barrier, which is critical to maintain the normal functions of the eye. Here, we report that JAM-C is highly expressed in retinal capillary endothelial cells (RCECs), and VEGF or PDGF-C treatment induced JAM-C translocation from the cytoplasm to the cytomembrane. Moreover, JAM-C knockdown in RCECs inhibited the adhesion and transmigration of macrophages from wet age-related macular degeneration (wAMD) patients to and through RCECs, whereas JAM-C overexpression in RCECs increased the adhesion and transmigration of macrophages from both wAMD patients and healthy controls. Importantly, the JAM-C overexpression-induced transmigration of macrophages from wAMD patients was abolished by the administration of the protein kinase C (PKC) inhibitor GF109203X. Of note, we found that the serum levels of soluble JAM-C were more than twofold higher in wAMD patients than in healthy controls. Mechanistically, we show that JAM-C overexpression or knockdown in RCECs decreased or increased cytosolic Ca2+ concentrations, respectively. Our findings suggest that the dynamic translocation of JAM-C induced by vasoactive molecules might be one of the mechanisms underlying inner endothelial BRB malfunction, and inhibition of JAM-C or PKC in RCECs may help maintain the normal function of the inner BRB. In addition, increased serum soluble JAM-C levels might serve as a molecular marker for wAMD, and modulating JAM-C activity may have potential therapeutic value for the treatment of BRB malfunction-related ocular diseases.
引用
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页数:12
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