...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cytokine >Induction of cardiac fibroblast lysyl oxidase by TGF-beta1 requires PI3K/Akt, Smad3, and MAPK signaling.
【24h】

Induction of cardiac fibroblast lysyl oxidase by TGF-beta1 requires PI3K/Akt, Smad3, and MAPK signaling.

机译：TGF-beta1诱导心脏成纤维细胞赖氨酰氧化酶需要PI3K / Akt，Smad3和MAPK信号传导。

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

Lysyl oxidase (LOX) is a key extracellular enzyme responsible for the post-translational modification of collagens I and III to form mature fibrillar collagen. Increased expression of LOX is associated with fibrosis and cardiac dysfunction, yet little is known about the regulation of LOX in the heart. In this study, the cell signaling pathways responsible for the regulation of LOX expression by transforming growth factor (TGF)-beta1 were assessed. Adult cardiac fibroblasts were isolated from male Sprague-Dawley rat hearts by enzymatic digestion. Fibroblasts were grown in DMEM with 10% FBS until approximately 80% confluent, growth arrested for 24h, and then treated with TGF-beta1 (0-10 ng/ml), in the absence or presence of inhibitors of (1) PI3K (wortmannin), (2) Smad3 (SIS3), (3) p38-MAPK (PD169316), (4) JNK (SP600125) and (5) ERK1/2 (PD98059). TGF-beta1 treatment significantly upregulated LOX mRNA and protein expression in cardiac fibroblasts, as well as activity in the cell-conditioned media. Concomitant increases in collagen types I and III, and bone morphogenic protein (BMP-1) expression were found in response to TGF-beta1. The increase of LOX protein in response to TGF-beta1 was prevented by inhibitors of PI3K, Smad3, p38-MAPK, JNK and ERK1/2. Blockade of PI3K also decreased TGF-beta1 induced phosphorylation of Smad3, suggesting that the PI3K/Akt and Smad pathways may be integrated in TGF-beta1 signaling. Further studies are warranted to address the regulation of LOX in the normal and diseased heart, and how this critical extracellular enzyme may be targeted for clinical benefit.
机译：赖氨酰氧化酶（LOX）是关键的细胞外酶，负责胶原I和III的翻译后修饰，形成成熟的原纤维胶原。 LOX的表达增加与纤维化和心脏功能障碍有关，但对心脏中LOX的调节知之甚少。在这项研究中，评估了通过转化生长因子（TGF）-beta1来调节LOX表达的细胞信号通路。通过酶消化从雄性Sprague-Dawley大鼠心脏分离成年心脏成纤维细胞。在不存在或存在（1）PI3K（渥曼青霉素）抑制剂的情况下，将成纤维细胞在含10％FBS的DMEM中生长，直到约80％汇合，生长停止24h，然后用TGF-beta1（0-10 ng / ml）处理），（2）Smad3（SIS3），（3）p38-MAPK（PD169316），（4）JNK（SP600125）和（5）ERK1 / 2（PD98059）。 TGF-beta1处理显着上调了心脏成纤维细胞中的LOX mRNA和蛋白表达以及细胞条件培养基中的活性。伴随着I型和III型胶原蛋白的增加，以及对TGF-beta1的反应，发现了骨形态发生蛋白（BMP-1）的表达。 PI3K，Smad3，p38-MAPK，JNK和ERK1 / 2的抑制剂阻止了LOX蛋白对TGF-β1的响应。 PI3K的封锁还减少了TGF-beta1诱导的Smad3磷酸化，表明PI3K / Akt和Smad途径可能整合在TGF-beta1信号传导中。有必要进行进一步的研究，以解决正常和患病心脏中LOX的调节，以及如何将这种关键的细胞外酶作为临床获益的靶点。

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