Back to Search
Start Over
Role of Junctional Adhesion Molecule-C in the Regulation of Inner Endothelial Blood-Retinal Barrier Function
- Source :
- Frontiers in Cell and Developmental Biology, Frontiers in Cell and Developmental Biology, Vol 9 (2021)
- Publication Year :
- 2021
- Publisher :
- Frontiers Media SA, 2021.
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
blood-retinal barrier
QH301-705.5
education
platelet-derived growth factor-C
Blood–retinal barrier
Cell and Developmental Biology
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Downregulation and upregulation
medicine
030212 general & internal medicine
Biology (General)
Protein kinase C
Original Research
retinal capillary endothelial cell
Gene knockdown
vascular endothelial growth factor
Chemistry
fungi
Cell Biology
humanities
Cell biology
Vascular endothelial growth factor
Cytosol
030104 developmental biology
Choroidal neovascularization
medicine.anatomical_structure
junctional adhesion molecule-C
cardiovascular system
sense organs
medicine.symptom
Junctional Adhesion Molecule C
Developmental Biology
Subjects
Details
- ISSN :
- 2296634X
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Frontiers in Cell and Developmental Biology
- Accession number :
- edsair.doi.dedup.....773ce69cdbfd054bc211003383f3a0ca