1. Academic Validation
  2. EPSTI1 promotes monocyte adhesion to endothelial cells in vitro via upregulating VCAM-1 and ICAM-1 expression

EPSTI1 promotes monocyte adhesion to endothelial cells in vitro via upregulating VCAM-1 and ICAM-1 expression

  • Acta Pharmacol Sin. 2022 Jul 1. doi: 10.1038/s41401-022-00923-5.
Yan-Rou Bei  # 1 Shun-Chi Zhang  # 2 Yu Song 3 Mao-Lin Tang 3 Ke-Lan Zhang 3 Min Jiang 3 Run-Chao He 3 Shao-Guo Wu 2 Xue-Hui Liu 1 2 Li-Mei Wu 2 Xiao-Yan Dai 4 Yan-Wei Hu 5 6
Affiliations

Affiliations

  • 1 Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
  • 2 Department of Clinical Laboratory, Guangzhou Twelfth People's Hospital, Guangzhou Medical University, Guangzhou, 510620, China.
  • 3 Department of Clinical Laboratory, Guangzhou Women & Children Medical Center, Guangzhou Medical University, Guangzhou, 510620, China.
  • 4 Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China. [email protected].
  • 5 Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. [email protected].
  • 6 Department of Clinical Laboratory, Guangzhou Women & Children Medical Center, Guangzhou Medical University, Guangzhou, 510620, China. [email protected].
  • # Contributed equally.
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.

Keywords

EPSTI1; ICAM-1; VCAM-1; atherosclerosis; monocyte-endothelial cell adhesion; p65.

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