期刊
PLOS ONE
卷 7, 期 10, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0046510
关键词
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资金
- National Natural Science Foundation of China [81020108031, 30572202, 30973558, 30772571, 30901815, 30901803]
- Ministry of Science and Technology in China [2009ZX09103-144]
- Ministry of Education of China (111 Projects) [B07001]
Background: Anti-angiogenic activity is considered to play a key role in the statin-induced anti-tumor effects. We aimed to identify new targets underlying this pleiotropic effect of lovastatin. Methodology/Principal Findings: We investigated the inhibitory effects of lovastatin on endothelial cell biology and angiogenesis in vitro. Lovastatin at high doses inhibited endothelial cell migration and tube formation. Using two-dimensional gel electrophoresis followed by mass spectrometry, we identified the up-regulation of the actin-binding protein transgelin 2 in endothelial cells following treatment with lovastatin. Changes in transgelin 2 levels were confirmed by Western blot and confocal microscopy. We further demonstrated that the Rho signaling inactivation and actin depolymerization contributed to the up-regulation of transgelin 2. The knockdown of transgelin 2 by siRNA dramatically enhanced endothelial migration and tube formation, and meanwhile attenuated the inhibitory effects of lovastatin on cell motility. Moreover, the lovastatin-induced inhibition of myosin light chain phosphorylation was also reversed by transgelin 2 knockdown. The activation of Rho GTPase in the absence of transgelin 2 may represent a mechanism underlying the regulation of phosphorylated myosin light chain by transgelin 2. Conclusions/Significance: These results strongly imply a novel role for transgelin 2 in the angiostatic activities of lovastatin.
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