Rev-erbalpha upregulates NF-kappaB-responsive genes in vascular smooth muscle cells

Hideyuki Migita; John Morser; Kohichi Kawai

doi:10.1016/S0014-5793(04)00118-8

Rev-erbalpha upregulates NF-kappaB-responsive genes in vascular smooth muscle cells

FEBS Lett. 2004 Mar 12;561(1-3):69-74. doi: 10.1016/S0014-5793(04)00118-8.

Authors

Hideyuki Migita¹, John Morser, Kohichi Kawai

Affiliation

¹ Cardiovascular Research, Drug Discovery Institute, Nihon Schering K.K., 1900-1, Togo Mobara, Chiba 297-0017, Japan. hmigita@schering.co.jp

PMID: 15013753
DOI: 10.1016/S0014-5793(04)00118-8

Abstract

Rev-erbalpha and retinoic acid receptor-related orphan receptor-alpha (RORalpha) are orphan nuclear receptors but their effects on transcription are opposed. Here, we show that Rev-erbalpha was expressed predominantly in vascular smooth muscle cells (VSMCs) rather than endothelial cells. Overexpression of Rev-erbalpha upregulated the expression of interleukin-6 and cyclooxygenase-2, and increased transactivation by NF-kappaB and translocation of p65 to the nucleus in A7r5 VSMCs. Furthermore, the expression of Rev-erbalpha was upregulated by RORalpha1 but that upregulation was attenuated by Rev-erbalpha itself in A7r5 VSMCs. These results suggest a regulatory link between Rev-erbalpha and the NF-kappaB pathway.

MeSH terms

Aorta / cytology
Cyclooxygenase 2
DNA-Binding Proteins / biosynthesis
DNA-Binding Proteins / metabolism
DNA-Binding Proteins / physiology*
Humans
Inflammation
Interleukin-6 / biosynthesis
Isoenzymes / biosynthesis
Membrane Proteins
Muscle, Smooth, Vascular / cytology*
Muscle, Smooth, Vascular / metabolism
Myocytes, Smooth Muscle / metabolism
NF-kappa B / genetics*
NF-kappa B / metabolism
Nuclear Receptor Subfamily 1, Group D, Member 1
Nuclear Receptor Subfamily 1, Group F, Member 1
Prostaglandin-Endoperoxide Synthases / biosynthesis
Receptor Cross-Talk
Receptors, Cytoplasmic and Nuclear / biosynthesis
Receptors, Cytoplasmic and Nuclear / metabolism
Receptors, Cytoplasmic and Nuclear / physiology*
Tissue Distribution
Trans-Activators / physiology*
Transcription Factor RelA
Transcriptional Activation
Umbilical Veins / cytology
Up-Regulation

Substances

DNA-Binding Proteins
Interleukin-6
Isoenzymes
Membrane Proteins
NF-kappa B
NR1D1 protein, human
Nuclear Receptor Subfamily 1, Group D, Member 1
Nuclear Receptor Subfamily 1, Group F, Member 1
RORA protein, human
Receptors, Cytoplasmic and Nuclear
Trans-Activators
Transcription Factor RelA
Cyclooxygenase 2
PTGS2 protein, human
Prostaglandin-Endoperoxide Synthases