| A Dominant-Negative PPARgamma Mutant Promotes Cell Cycle Progression and Cell Growth in Vascular Smooth Muscle Cells. | |
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MedLine Citation:
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PMID: 20300579 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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PPARgamma ligands have been shown to have antiproliferative effects on many cell types. We herein report that a synthetic dominant-negative (DN) PPARgamma 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-PPARgamma promoted G1-->S cell cycle progression, enhanced BrdU incorporation, and increased cell proliferation. DN-PPARgamma 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) PPARgamma inhibited cell cycle progression and the activity and expression of positive regulators of the cell cycle. DN-PPARgamma expression, however, did not up-regulate positive cell cycle regulators in PPARgamma-deficient cells, strongly suggesting that DN-PPARgamma effects on cell cycle result from blocking the function of endogenous wild-type PPARgamma. DN-PPARgamma expression enhanced phosphorylation of ERK MAPKs. Furthermore, the ERK specific-inhibitor PD98059 blocked DN-PPARgamma-induced phosphorylation of Rb and expression of cyclin A and MCM7. Our data thus suggest that DN-PPARgamma 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). |
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Authors:
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Joey Z Liu; Christopher J Lyon; Willa A Hsueh; Ronald E Law |
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Publication Detail:
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Type: Journal Article Date: 2010-03-10 |
Journal Detail:
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Title: PPAR research Volume: 2009 ISSN: 1687-4765 ISO Abbreviation: PPAR Res Publication Date: 2009 |
Date Detail:
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Created Date: 2010-03-19 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101269101 Medline TA: PPAR Res Country: United States |
Other Details:
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Languages: eng Pagination: 438673 Citation Subset: - |
Affiliation:
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The Methodist Hospital Research Institute, Houston, TX 77030, USA. |
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