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Tim-3 promotes tube formation and decreases tight junction formation in vascular endothelial cells

Cong, Yizi, Wang, Xingmiao, Wang, Suxia, Qiao, Guangdong, Li, Yalun, Cao, Jianqiao, Jiang, Wen G. and Cui, Yuxin 2020. Tim-3 promotes tube formation and decreases tight junction formation in vascular endothelial cells. Bioscience Reports 40 (10) , BSR20202130. 10.1042/BSR20202130
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Abstract

As a negative immune checkpoint molecule, T cell immunoglobulin domain and mucin domain containing molecule-3 (Tim-3) has been found to serve a crucial role in immune escape and tumour progression. Previous studies have reported that Tim-3 is important to endothelial cells and it has also been demonstrated to be involved in numerous types of human disease, including melanoma, lymphoma, rickettsial infection and atherosclerosis; however, its exact mechanism of action remains largely unknown. In the present study, Tim-3 was overexpressed in vascular endothelial HMVECs and HUVECs and in vitro assays were used to determine that Tim-3 promoted cell proliferation, migration, invasion and tube formation through activating cyclin D1, Ras homolog gene family member A and vascular endothelial growth factor receptor 2 (VEGFR2). Additionally, Tim-3 decreased tight junction (TJ) formation and the transepithelial resistance of endothelial cells by decreasing the expression levels of TJ protein 2, Occludin and claudin 1. In conclusion, these findings suggested that Tim-3 may exert a positive role in angiogenesis and a negative role in TJ formation in vascular endothelial cells, which may provide novel strategies for the treatment of Tim-3 associated diseases.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Portland Press
ISSN: 0144-8463
Funders: Cardiff China Medical Scholarship, the key project of research and devel¬opment plan of Shandong province (No.2018GSF118125) and Yantai city (No.2017YD007)
Date of First Compliant Deposit: 6 October 2020
Date of Acceptance: 2 October 2020
Last Modified: 03 Nov 2020 14:28
URI: http://orca-mwe.cf.ac.uk/id/eprint/135325

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