A Dominant-Negative PPARγ Mutant Promotes Cell Cycle Progression and Cell Growth in Vascular Smooth Muscle Cells
Joint Authors
Law, Ronald E.
Hsueh, Willa A.
Lyon, Christopher J.
Liu, Joey Z.
Source
Issue
Vol. 2009, Issue 2009 (31 Dec. 2009), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2010-03-10
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Natural & Life Sciences (Multidisciplinary)
Biology
Abstract EN
PPARγ ligands have been shown to have antiproliferative effects on many cell types.
We herein report that a synthetic dominant-negative (DN) PPARγ mutant functions like a growth factor to promote cell cycle progression and cell proliferation in human coronary artery smooth muscle cells (CASMCs).
In quiescent CASMCs, adenovirus-expressed DN-PPARγ promoted G1→S cell cycle progression, enhanced BrdU incorporation, and increased cell proliferation.
DN-PPARγ expression also markedly enhanced positive regulators of the cell cycle, increasing Rb and CDC2 phosphorylation and the expression of cyclin A, B1, D1, and MCM7.
Conversely, overexpression of wild-type (WT) or constitutively-active (CA) PPARγ inhibited cell cycle progression and the activity and expression of positive regulators of the cell cycle.
DN-PPARγ expression, however, did not up-regulate positive cell cycle regulators in PPARγ-deficient cells, strongly suggesting that DN-PPARγ effects on cell cycle result from blocking the function of endogenous wild-type PPARγ.
DN-PPARγ expression enhanced phosphorylation of ERK MAPKs.
Furthermore, the ERK specific-inhibitor PD98059 blocked DN-PPARγ-induced phosphorylation of Rb and expression of cyclin A and MCM7.
Our data thus suggest that DN-PPARγ promotes cell cycle progression and cell growth in CASMCs by modulating fundamental cell cycle regulatory proteins and MAPK mitogenic signaling pathways in vascular smooth muscle cells (VSMCs).
American Psychological Association (APA)
Liu, Joey Z.& Lyon, Christopher J.& Hsueh, Willa A.& Law, Ronald E.. 2010. A Dominant-Negative PPARγ Mutant Promotes Cell Cycle Progression and Cell Growth in Vascular Smooth Muscle Cells. PPAR Research،Vol. 2009, no. 2009, pp.1-10.
https://search.emarefa.net/detail/BIM-472371
Modern Language Association (MLA)
Liu, Joey Z.…[et al.]. A Dominant-Negative PPARγ Mutant Promotes Cell Cycle Progression and Cell Growth in Vascular Smooth Muscle Cells. PPAR Research No. 2009 (2009), pp.1-10.
https://search.emarefa.net/detail/BIM-472371
American Medical Association (AMA)
Liu, Joey Z.& Lyon, Christopher J.& Hsueh, Willa A.& Law, Ronald E.. A Dominant-Negative PPARγ Mutant Promotes Cell Cycle Progression and Cell Growth in Vascular Smooth Muscle Cells. PPAR Research. 2010. Vol. 2009, no. 2009, pp.1-10.
https://search.emarefa.net/detail/BIM-472371
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-472371