• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cellular Signalling >Phosphatidylinositol 3-kinase/Akt pathway is involved in transforming growth factor-beta 1-induced phenotypic modulation of 10T1/2 cells to smooth muscle cells
【24h】

Phosphatidylinositol 3-kinase/Akt pathway is involved in transforming growth factor-beta 1-induced phenotypic modulation of 10T1/2 cells to smooth muscle cells

机译：磷脂酰肌醇3-激酶/ Akt通路参与将生长因子β1诱导的10T1 / 2细胞表型调节转化为平滑肌细胞

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Transforming growth factor-beta 1 (TGF-beta 1) is known to induce phenotypic modulation of mesenchymal cells to SMCs. However, the intracellular signals regulating induction of the SMC phenotype of mesenchymal cells have not been fully clarified. In the present study, we examined the role of the mitogen-activated protein kinase (MAPK) superfamily and phosphatidylinositol. 3-kinase (P13K)/Akt in the TGF-beta 1 mediated phenotypic modulation of 10T1/2 mesenchymal cells to SMCs characterized by the expression of SMC-specific markers, including smooth muscle alpha-actin (SM alpha-actin), myosin heavy chain(SM-NMC),and protein 22-alpha(SM22 alpha). The results showed the following: (1) TGF-beta 1 induced SM alpha-actin and SM-MHC expressions in 10T1/2 cells in a time-dependent manner. (2) TGF-beta 1 induced biphasic increases in extracellular signal-regulated kinase (ERK), p38 MAPK, c-Jun-NH2-terminal kinase (JNK), and Akt phosphorylation. (3) The inhibitor for P13K/Akt (i.e., LY294002), but not those for MAPKs (i.e.,S13203580,PLD98059, and SP600125), attenuated the TGF-beta 1-induced SM alpha-actin and SM-NMC expressions in 10T1/2 cells; in addition, transfection of 10T1/2 cells with the Akt-specific small interfering RNA (siRNA) significantly reduced their SM alpha-actin and SM-MHC expressions. (4) LY294002 and the Akt-specific siRNA inhibited the TGF-beta 1-induced SM22 alpha gene expression and promoter activity, suggesting that the TGF-beta 1-induced gene expression was mediated by P13K/Akt at the transcriptional level. (5) LY294002 inhibited the TGF-beta 1-induced gene expression and DNA binding activity of serum response factor (SRF). These results indicate that TGF-beta 1 is capable of inducing the SMC phenotype of 10T1/2 cells and that this induction is mediated through the P13K/Akt signaling pathway. (c) 2005 Elsevier Inc. All rights reserved.
机译：已知转化生长因子-beta 1（TGF-beta 1）诱导间充质细胞向SMCs的表型调节。但是，调节间充质细胞SMC表型诱导的细胞内信号尚未完全阐明。在本研究中，我们检查了有丝分裂原激活的蛋白激酶（MAPK）超家族和磷脂酰肌醇的作用。 TGF-beta 1介导的10T1 / 2间充质细胞向SMC的表型调节中的3-激酶（P13K）/ Akt，其特征为SMC特异性标志物的表达，包括平滑肌α-肌动蛋白（SM alpha-actin），肌球蛋白重链（SM-NMC）和蛋白质22-alpha（SM22 alpha）。结果显示以下结果：（1）TGF-beta 1诱导10T1 / 2细胞中SMα-肌动蛋白和SM-MHC表达呈时间依赖性。 （2）TGF-beta 1诱导细胞外信号调节激酶（ERK），p38 MAPK，c-Jun-NH2-末端激酶（JNK）和Akt磷酸化双相增加。 （3）P13K / Akt抑制剂（即LY294002）而不是MAPK抑制剂（即S13203580，PLD98059和SP600125）的抑制剂减弱了10T1中TGF-beta 1诱导的SMα-肌动蛋白和SM-NMC的表达。 / 2格;此外，用Akt特异性小干扰RNA（siRNA）转染10T1 / 2细胞可显着降低其SMα-肌动蛋白和SM-MHC表达。 （4）LY294002和Akt特异性siRNA抑制了TGF-β1诱导的SM22α基因表达和启动子活性，提示TGF-β1诱导的基因表达在转录水平上由P13K / Akt介导。 （5）LY294002抑制TGF-β1诱导的血清反应因子（SRF）基因表达和DNA结合活性。这些结果表明，TGF-beta 1能够诱导10T1 / 2细胞的SMC表型，并且这种诱导是通过P13K / Akt信号传导途径介导的。 （c）2005 Elsevier Inc.保留所有权利。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号