title: A novel inhibitory mechanism of MRTF-A/B on the ICAM-1 gene expression in vascular endothelial cells.
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-κB (NF-κB) plays a key role in ICAM-1 gene transcription. However, nuclear accumulation of NF-κB 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 NF-κB 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.affiliation: Department of RNA Biology and Neuroscience, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Ken'ichiro
authors.initials: K
authors.lastname: Hayashi
authors.affiliation: Department of RNA Biology and Neuroscience, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Murai
authors.affiliation: Department of Pathology, School of Medicine, Iwate Medical University, Yahaba-Cho, Shiwa-Gun, Iwate 028-3694, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Oikawa
authors.affiliation: Department of Pathology, School of Medicine, Iwate Medical University, Yahaba-Cho, Shiwa-Gun, Iwate 028-3694, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Masuda
authors.affiliation: Department of Ophthalmology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, 755-8505, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kimura
authors.affiliation: Walther Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Muehlich
authors.affiliation: Department of Biological Sciences, Columbia University, New York, USA.
authors.forename: Ron
authors.initials: R
authors.lastname: Prywes
authors.affiliation: Department of RNA Biology and Neuroscience, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Morita
mesh_terms: D000577:Amides / Q000494:pharmacology; D000818:Animals; D002450:Cell Communication; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000577:Amides; D008070:Lipopolysaccharides; C511173:Mrtfa protein, mouse; D016328:NF-kappa B; D011725:Pyridines; D015534:Trans-Activators; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; C503315:myocardin-related transcription factor B, mouse; D018799:Intercellular Adhesion Molecule-1; C108830:Y 27632; D048049:Extracellular Signal-Regulated MAP Kinases