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
来源
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY | 2021年 / 9卷
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
收藏
页数:12
相关论文
共 50 条
  • [1] A Novel Function of Junctional Adhesion Molecule-C in Mediating Melanoma Cell Metastasis
    Langer, Harald F.
    Orlova, Valeria V.
    Xie, Changping
    Kaul, Sunil
    Schneider, Darius
    Lonsdorf, Anke S.
    Fahrleitner, Manuela
    Choi, Eun Young
    Dutoit, Vanessa
    Pellegrini, Manuela
    Grossklaus, Sylvia
    Nawroth, Peter P.
    Baretton, Gustavo
    Santoso, Sentot
    Hwang, Sam T.
    Arnold, Bernd
    Chavakis, Triantafyllos
    CANCER RESEARCH, 2011, 71 (12) : 4096 - 4105
  • [2] Endothelial-specific deficiency of Junctional Adhesion Molecule-C promotes vessel normalisation in proliferative retinopathy
    Economopoulou, Matina
    Avramovic, Nemanja
    Klotzsche-von Ameln, Anne
    Korovina, Irina
    Sprott, David
    Samus, Maryna
    Gercken, Bettina
    Troullinaki, Maria
    Grossklaus, Sylvia
    Funk, Richard H.
    Li, Xuri
    Imhof, Beat A.
    Orlova, Valeria V.
    Chavakis, Triantafyllos
    THROMBOSIS AND HAEMOSTASIS, 2015, 114 (06) : 1241 - 1250
  • [3] Inner Blood-Retinal Barrier Regulation in Retinopathies
    Hudson, Natalie
    Campbell, Matthew
    RETINAL DEGENERATIVE DISEASES: MECHANISMS AND EXPERIMENTAL THERAPY, 2019, 1185 : 329 - 333
  • [4] The role of junctional adhesion molecule-C in trophoblast differentiation and function during normal pregnancy and preeclampsia
    Cao, Chenrui
    Dai, Yimin
    Wang, Zhiyin
    Zhao, Guangfeng
    Duan, Honglei
    Zhu, Xiangyu
    Wang, Jingmei
    Zheng, Mingming
    Weng, Qiao
    Wang, Limin
    Gou, Wenjing
    Zhang, Haili
    Li, Chanjuan
    Liu, Dan
    Hu, Yali
    PLACENTA, 2022, 118 : 55 - 65
  • [5] Neuronal Expression of Junctional Adhesion Molecule-C is Essential for Retinal Thickness and Photoreceptor Survival
    Li, Y.
    Zhang, F.
    Lu, W.
    Li, X.
    CURRENT MOLECULAR MEDICINE, 2017, 17 (07) : 497 - 508
  • [6] The molecular structure and function of the inner blood-retinal barrier
    Thomas W. Gardner
    David A. Antonetti
    Alistair J. Barber
    Erich Lieth
    John A. Tarbell
    Documenta Ophthalmologica, 1999, 97 : 229 - 237
  • [7] The molecular structure and function of the inner blood-retinal barrier
    Gardner, TW
    Antonetti, DA
    Barber, AJ
    Lieth, E
    Tarbell, JA
    DOCUMENTA OPHTHALMOLOGICA, 1999, 97 (3-4) : 229 - 237
  • [8] Novel distribution of junctional adhesion molecule-C in the neural retina and retinal pigment epithelium
    Daniele, Lauren L.
    Adams, Ralf H.
    Durante, Diane E.
    Pugh, Edward N., Jr.
    Philp, Nancy J.
    JOURNAL OF COMPARATIVE NEUROLOGY, 2007, 505 (02) : 166 - 176
  • [9] Junctional Adhesion Molecule-C Is a Soluble Mediator of Angiogenesis
    Rabquer, Bradley J.
    Amin, Mohammad A.
    Teegala, Nanditha
    Shaheen, Matthew K.
    Tsou, Pei-Suen
    Ruth, Jeffrey H.
    Lesch, Charles A.
    Imhof, Beat A.
    Koch, Alisa E.
    JOURNAL OF IMMUNOLOGY, 2010, 185 (03) : 1777 - 1785
  • [10] Transcriptional induction of junctional adhesion molecule-C gene expression in activated T cells
    Immenschuh, Stephan
    Naidu, Srivatsava
    Chavakis, Triantafyllos
    Beschmann, Heike
    Ludwig, Ralf J.
    Santoso, Sentot
    JOURNAL OF LEUKOCYTE BIOLOGY, 2009, 85 (05) : 796 - 803