Transgelin 2 participates in lovastatin-induced anti-angiogenic effects in endothelial cells through a phosphorylated myosin light chain-related mechanism.
Transgelin 2 participates in lovastatin-induced anti-angiogenic effects in endothelial cells through a phosphorylated myosin light chain-related mechanism.
复制标题
Transgelin 2 通过磷酸化肌球蛋白轻链相关机制参与洛伐他汀诱导的内皮细胞抗血管生成作用
DOI：
10.1371/journal.pone.0046510
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Xiao Y;Li Y;Han J;Pan Y;Tie L;Li X
背景抗血管生成活性被认为在他汀类药物诱导的抗肿瘤效应中起关键作用。我们的目的是确定新的目标，这种多效作用的洛伐他汀。方法学/主要发现我们研究了洛伐他汀对体外内皮细胞生物学和血管生成的抑制作用。高剂量洛伐他汀抑制内皮细胞迁移和管形成。使用二维凝胶电泳，然后质谱，我们确定了上调肌动蛋白结合蛋白transgelin 2在内皮细胞治疗后，洛伐他汀。transgelin 2水平的变化通过Western印迹和共聚焦显微镜证实。我们进一步证明了Rho信号的失活和肌动蛋白的解聚有助于transgelin 2的上调。通过siRNA敲低transgelin 2显著增强内皮细胞迁移和管腔形成，同时减弱洛伐他汀对细胞运动的抑制作用。此外，lovastatin诱导的抑制肌球蛋白轻链磷酸化也逆转transgelin 2敲低。在缺乏transgelin 2的情况下Rho GT3的激活可能代表transgelin 2调节磷酸化肌球蛋白轻链的潜在机制。结论/意义这些结果强烈暗示了transgelin 2在洛伐他汀的血管抑制活性中的新作用。
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.
登录
查看更多内容
影响因子：
2.9
作者：
DUBAND, JL;GIMONA, M;SMALL, JV
通讯作者：
SMALL, JV
影响因子：
4.8
作者：
Amano, M;Ito, M;Kaibuchi, K
通讯作者：
Kaibuchi, K
影响因子：
37.8
作者：
Weis, M;Heeschen, C;Cooke, JP
通讯作者：
Cooke, JP
影响因子：
2.7
作者：
ABE, M;TAKAHASHI, K;HIWADA, K
通讯作者：
HIWADA, K
影响因子：
5.4
作者：
Chen, Jie;Watanabe, Masami;Kumon, Hiromi
通讯作者：
Kumon, Hiromi