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Trichostatin A enhances proliferation and migration of vascular smooth muscle cells by downregulating thioredoxin 1
- Title
- Trichostatin A enhances proliferation and migration of vascular smooth muscle cells by downregulating thioredoxin 1
- Authors
- Song S.; Kang S.W.; Choi C.
- Ewha Authors
- 강상원
- SCOPUS Author ID
- 강상원
- Issue Date
- 2010
- Journal Title
- Cardiovascular Research
- ISSN
- 0008-6363
- Citation
- Cardiovascular Research vol. 85, no. 1, pp. 241 - 249
- Indexed
- SCI; SCIE; SCOPUS
- Document Type
- Article
- Abstract
- AimsA reduction in the level of thioredoxin 1 (Trx1) has been proposed as a possible mechanism for the tumor-specific growth arrest caused by inhibition of histone deacetylases (HDACs). In this study, we investigated the effect of trichostatin A (TSA), a potent HDAC inhibitor, on the proliferation and migration of vascular smooth muscle cells (VSMCs), and we examined the role of reduced Trx1 levels in this effect.Methods and resultsTSA treatment time-dependently decreased Trx1 expression in rat VSMCs at both the mRNA and protein levels. It also enhanced platelet-derived growth factor (PDGF)-induced proliferation and migration of the VSMCs. By potentiating Akt phosphorylation, the siRNA-induced downregulation of Trx1 also enhanced VSMC proliferation and migration in response to PDGF or serum treatment. Consistent with these results, TSA administration increased neointimal thickening in a murine model of post-angioplastic restenosis.ConclusionThese data demonstrate that TSA enhances vascular proliferative activity by downregulating Trx1, thus activating an Akt-dependent pathway. Our results indicate that, in addition to its apoptotic effects in tumour cells, the downregulation of Trx1 has a proliferative role in primary VSMCs.
- DOI
- 10.1093/cvr/cvp263
- Appears in Collections:
- 자연과학대학 > 생명과학전공 > Journal papers
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