A novel inhibitory mechanism of MRTF-A/B on the ICAM-1 gene expression in vascular endothelial cells

Hayashi K, Murai T, Oikawa H, Masuda T, Kimura K, Muehlich S, Prywes R, Morita T (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Scientific Reports Nature Publishing Group: Open Access Journals - Option B

Book Volume: 5

Article Number: 10627

DOI: 10.1038/srep10627

Abstract

The roles of myocardin-related transcription factor A (MRTF-A) and MRTF-B in vascular endothelial cells are not completely understood. Here, we found a novel regulatory mechanism for MRTF-A/B function. MRTF-A/B tend to accumulate in the nucleus in arterial endothelial cells in vivo and human aortic endothelial cells (HAoECs) in vitro. In HAoECs, nuclear localization of MRTF-A/B was not significantly affected by Y27632 or latrunculin B, primarily due to the reduced binding of MRTF-A/B to G-actin and in part, to the low level of MRTF-A phosphorylation by ERK. MRTF-A/B downregulation by serum depletion or transfection of siRNA against MRTF-A and/or MRTF-B induced ICAM-1 expression in HAoECs. It is known that nuclear import of nuclear factor κ B (NFκ B) plays a key role in ICAM-1 gene transcription. However, nuclear accumulation of NFκ B p65 was not observed in MRTF-A/B-depleted HAoECs. Our present findings suggest that MRTF-A/B inhibit ICAM-1 mRNA expression by forming a complex with NFκ B p65 in the nucleus. Conversely, downregulation of MRTF-A/B alleviates this negative regulation without further translocation of NF κB p65 into the nucleus. These results reveal the novel roles of MRTF-A/B in the homeostasis of vascular endothelium.

Authors with CRIS profile

Susanne Mühlich

Involved external institutions

Iwate Medical University JP Japan (JP) Yamaguchi University JP Japan (JP) Ludwig-Maximilians-Universität (LMU) DE Germany (DE) Columbia University US United States (USA) (US)

How to cite

APA:

Hayashi, K., Murai, T., Oikawa, H., Masuda, T., Kimura, K., Muehlich, S.,... Morita, T. (2015). A novel inhibitory mechanism of MRTF-A/B on the ICAM-1 gene expression in vascular endothelial cells. Scientific Reports, 5. https://doi.org/10.1038/srep10627

MLA:

Hayashi, Ken'Ichiro, et al. "A novel inhibitory mechanism of MRTF-A/B on the ICAM-1 gene expression in vascular endothelial cells." Scientific Reports 5 (2015).

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