1. Transcription factor Ap-1 mediates proangiogenic MIF expression in human endothelial cells exposed to Angiotensin II.
- Author
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Shan ZX, Lin QX, Yang M, Zhang B, Zhu JN, Mai LP, Deng CY, Liu JL, Zhang YY, Lin SG, and Yu XY
- Subjects
- Animals, Base Sequence, Cell Extracts, Cell Nucleus drug effects, Cell Nucleus metabolism, Electrophoretic Mobility Shift Assay, Humans, Macrophage Migration-Inhibitory Factors genetics, Macrophage Migration-Inhibitory Factors pharmacology, Molecular Sequence Data, Rats, Umbilical Veins cytology, Angiogenesis Inducing Agents metabolism, Angiotensin II pharmacology, Endothelial Cells drug effects, Endothelial Cells metabolism, Macrophage Migration-Inhibitory Factors metabolism, Neovascularization, Physiologic drug effects, Transcription Factor AP-1 metabolism
- Abstract
Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine associated with the atherosclerotic process and atherosclerotic plaque stability. MIF was shown to be highly expressed in advanced atherosclerotic lesions. Neutralizing MIF with a blocking antibody induced a regression of established atherosclerotic lesions. In this study, we investigated the mechanism underlying the proangiogenic effect of MIF in human umbilical vein endothelial cells (HUVECs). We showed that MIF induced the expression of angiogenesis-related genes in HUVECs. We also showed that MIF induced tube formation of HUVECs in vitro and in vivo. Angiotensin II (Ang II) could specifically up-regulate MIF expression in HUVECs. Using a luciferase reporter assay, we demonstrated that the AP-1 response element in the 5'-UTR of the MIF gene played a role in Ang II-induced MIF expression. Small hairpin RNA (shRNA) targeting c-Jun, a component of AP-1, and the AP-1 inhibitor CHX both efficiently inhibited MIF expression. The consistent result of electrophoretic mobility shift assay (EMSA) showed that Ang II specifically increased AP-1 activation in HUVECs. Our results suggest that AP-1 mediates Ang II-induced MIF expression which contributes to atherosclerotic plaque destabilization in human endothelial cells., (Copyright © 2010 Elsevier Ltd. All rights reserved.)
- Published
- 2011
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