Abstract
Atherosclerosis is a chronic inflammatory disease of arterial wall, and circulating monocyte adhesion to endothelial cells is a crucial step in the pathogenesis of atherosclerosis. Epithelial-stromal interaction 1 (EPSTI1) is a novel gene, which is dramatically induced by epithelial-stromal interaction in human breast cancer. EPSTI1 expression is not only restricted to the breast but also in other normal tissues. In this study we investigated the role of EPSTI1 in monocyte-endothelial cell adhesion and its expression pattern in atherosclerotic plaques. We showed that EPSTI1 was dramatically upregulated in human and mouse atherosclerotic plaques when compared with normal arteries. In addition, the expression of EPSTI1 in endothelial cells of human and mouse atherosclerotic plaques is significantly higher than that of the normal arteries. Furthermore, we demonstrated that EPSTI1 promoted human monocytic THP-1 cell adhesion to human umbilical vein endothelial cells (HUVECs) via upregulating VCAM-1 and ICAM-1 expression in HUVECs. Treatment with LPS (100, 500, 1000 ng/mL) induced EPSTI1 expression in HUVECs at both mRNA and protein levels in a dose- and time-dependent manner. Knockdown of EPSTI1 significantly inhibited LPS-induced monocyte-endothelial cell adhesion via downregulation of VCAM-1 and ICAM-1. Moreover, we revealed that LPS induced EPSTI1 expression through p65 nuclear translocation. Thus, we conclude that EPSTI1 promotes THP-1 cell adhesion to endothelial cells by upregulating VCAM-1 and ICAM-1 expression, implying its potential role in the development of atherosclerosis.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (Grant numbers: 82072335, 81871701, 81974046, and 82170467), the Natural Science Fund of Guangdong Province (Grant numbers: 2020B1515020013 and 2018A030313533), Guangzhou Women and Children’s Medical Center (Grant number: GWCMC2020-6-010).
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XYD and YWH developed the study′s concept, designed the experiments, and wrote the manuscript; YRB and SCZ conducted the experiments and acquired data; YS, MLT, KLZ, and RCH analyzed data; MJ, XHL, LMW, and SGW revised the manuscript.
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Bei, Yr., Zhang, Sc., Song, Y. et al. EPSTI1 promotes monocyte adhesion to endothelial cells in vitro via upregulating VCAM-1 and ICAM-1 expression. Acta Pharmacol Sin 44, 71–80 (2023). https://doi.org/10.1038/s41401-022-00923-5
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DOI: https://doi.org/10.1038/s41401-022-00923-5
