Trichostatin A, an Inhibitor of Histone Deacetylase, Inhibits Smooth Muscle Cell Proliferation via Induction of p21'WAF1'
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Accession number;06A0638951
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| Title;Trichostatin A, an Inhibitor of Histone Deacetylase, Inhibits Smooth Muscle Cell Proliferation via Induction of p21'WAF1' |
| Author;
OKAMOTO HIROSHI
(Dep. of Internal Medicine, Kobe Univ. Graduate School of Medicine)
FUJIOKA YOSHIO
(Dep. of Internal Medicine, Kobe Univ. Graduate School of Medicine)
FUJIOKA YOSHIO
(Laboratory of Nutritional Physiology, Faculty of Nutrition, Kobegakuin University)
TAKAHASHI AKIHIRO
(Dep. of Internal Medicine, Kobe Univ. Graduate School of Medicine)
TAKAHASHI TOMOSABURO
(Dep. of Internal Medicine, Kobe Univ. Graduate School of Medicine)
TANIGUCHI TAKAHIRO
(Dep. of Internal Medicine, Kobe Univ. Graduate School of Medicine)
ISHIKAWA YUICHI
(Faculty of Health Sciences, Kobe University School of Medicine)
YOKOYAMA MITSUHIRO
(Dep. of Internal Medicine, Kobe Univ. Graduate School of Medicine)
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Journal Title;J Atheroscler Thromb
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Journal Code:L2187A
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ISSN:1340-3478
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VOL.13;NO.4;PAGE.183-191 (J-STAGE)(2006)
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| Figure&Table&Reference;FIG.6, REF.52 |
| Pub. Country;Japan |
| Language;English |
| Abstract;The proliferation of vascular smooth muscle cells (VSMCs) can contribute to a variety of pathological states, including atherosclerosis and post-angioplasty restenosis. The p21'WAF1' cyclin-dependent kinase inhibitor regulates cell-cycle progression, senescence, and differentiation in injured blood vessels. Histone deacetylase (HDAC) inhibitors have shown utility in controlling proliferation in a wide range of tumor cell lines, possibly by inducing the expression of p21'WAF1'. Our goal was to investigate the effect of trichostatin A (TSA), a specific and potent HDAC inhibitor, on the proliferation of vascular smooth muscle cells (VSMCs) isolated from rat thoracic aorta. TSA suppressed the HDAC activity of VSMCs in a dose-dependent manner and inhibited VSMC proliferation as demonstrated by cell number counting and the degree of ['3'H] thymidine incorporation. Further, TSA reduced the phosphorylation of Rb protein, a regulator of cell-cycle progression. TSA treatment also induced the expression of p21'WAF1' but not of p16'INK4', p27'KIP1' or p53. Finally, TSA inhibited HDAC activity of VSMCs from p21'WAF1' knock-out mice but had no effect on VSMC proliferation in these animals. In conclusion, TSA inhibits VSMC proliferation via the induction of p21'WAF1' expression and subsequent cell-cycle arrest with reduction of the phosphorylation of Rb protein at the G1-S phase. (Author abst.) |
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