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

Biosci Rep. 2020 Oct 30;40(10):BSR20202130. doi: 10.1042/BSR20202130.

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 diseases, 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 human lung microvascular endothelial cells (HMVECs) and human umbilical vein endothelial cells (HUVECs), and in vitro assays were used to determine that Tim-3 promoted cell proliferation, migration, invasion and tube formation through activating cyclin D1 (CCND1), Ras homolog gene family member A and vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2). Additionally, Tim-3 decreased tight junction (TJ) formation and the transepithelial resistance (TER) of endothelial cells by decreasing the expression levels of TJ protein 2, Occludin and claudin 1 (CLND1). 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.

Keywords: Tim-3; angiogenesis; endothelial cells; tight junction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Movement
  • Cell Proliferation
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / growth & development*
  • Endothelium, Vascular / metabolism
  • Hepatitis A Virus Cellular Receptor 2 / genetics
  • Hepatitis A Virus Cellular Receptor 2 / metabolism*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Lung / blood supply
  • Microvessels / cytology
  • Microvessels / growth & development
  • Microvessels / metabolism
  • Neovascularization, Physiologic*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Tight Junctions / metabolism*
  • Transfection

Substances

  • HAVCR2 protein, human
  • Hepatitis A Virus Cellular Receptor 2
  • Recombinant Proteins