Title
TR3 orphan receptor is expressed in vascular endothelial cells and mediates cell cycle arrest
Author
Arkenbout, E.K.
van Bragt, M.
Eldering, E.
van Bree, C.
Grimbergen, J.M.
Quax, P.H.A.
Pannekoek, H.
de Vries, C.J.M.
Gaubius Instituut TNO
Publication year
2003
Abstract
Objective - Endothelial cells play a pivotal role in vascular homeostasis. In this study, we investigated the function of the nerve growth factor-induced protein-B (NGFI-B) subfamily of nuclear receptors comprising the TR3 orphan receptor (TR3), mitogen-induced nuclear orphan receptor (MINOR), and nuclear orphan receptor of T cells (NOT) in endothelial cells. Methods and Results - The mRNA expression of TR3, MINOR, and NOT in atherosclerotic lesions was assessed in human vascular specimens. Each of these factors is expressed in smooth muscle cells, as described before, and in subsets of endothelial cells, implicating that they might affect endothelial cell function. Adenoviral overexpression of TR3 in cultured endothelial cells resulted in decreased [ 3H]thymidine incorporation, whereas a dominant-negative TR3 variant that inhibits the activity of endogenous TR3-like factors enhanced DNA synthesis. TR3 interfered with progression of the cell cycle by upregulating p27Kip1 and downregulating cyclin A, whereas expression levels of a number of other cell cycle-associated proteins remained unchanged. Conclusions - These findings demonstrate that TR3 is a modulator of endothelial cell proliferation and arrests endothelial cells in the G1 phase of the cell cycle by influencing cell cycle protein levels. We hypothesize involvement of TR3 in the maintenance of integrity of the vascular endothelium.
Subject
Biology
Biomedical Research
Endothelial cells
TR3 orphan receptor
Vascular biology
Cell nucleus receptor
Cyclin A
Messenger RNA
Mitogen induced nuclear orphan receptor
Nerve growth factor receptor
Nuclear orphan receptor of t cells
Protein
Protein subunit
Receptor subtype
Thymidine
Unclassified drug
Adenovirus
Atherosclerosis
Blood vessel
Controlled study
Down regulation
Endothelium cell
Gene expression
Gene overexpression
Human cell
Medical assessment
Nonhuman
Nucleotide sequence
Protein expression
Smooth muscle fiber
Upregulation
Virus culture
Adenoviridae
Cell Cycle
Cell Division
Cells, Cultured
DNA, Complementary
Endothelium, Vascular
Gene Expression Regulation
Gene Transfer Techniques
Humans
Peptides
Protein Structure, Tertiary
Receptors, Steroid
Receptors, Thyroid Hormone
Sequence Deletion
Stem Cells
Trans-Activation (Genetics)
Umbilical Veins
Variation (Genetics)
Virus Replication
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DOI
https://doi.org/10.1161/01.atv.0000084639.16462.7a
TNO identifier
237275
ISSN
1079-5642
Source
Arteriosclerosis, Thrombosis, and Vascular Biology, 23 (9), 1535-1540
Document type
article