Role of Smad2/3 and p38 MAP kinase in TGF-β1-induced epithelial-mesenchymal transition of pulmonary epithelial cells.
Role of Smad2/3 and p38 MAP kinase in TGF-β1-induced epithelial-mesenchymal transition of pulmonary epithelial cells.
复制标题
DOI：
10.1002/jcp.22448
复制
发表时间：
2011-05
影响因子：
5.6
通讯作者：
Kern, Jeffrey A.
中科院分区：
文献类型：
--
作者：
Kolosova, Irina;Nethery, David;Kern, Jeffrey A.
特发性肺纤维化以肌成纤维细胞聚集、细胞外基质（ECM）重塑和过度胶原沉积为特征。产生ECM的肌成纤维细胞可以通过上皮向间充质转化（EMT）起源于上皮细胞。TGF-β1在体内外均可诱导肺上皮细胞发生EMT，但其作用机制尚不清楚。我们推测TGF-β1通过Smad依赖和非依赖两种途径诱导EMT。为了验证这一假设，我们研究了TGF-β1诱导的Smad和p38丝裂原活化蛋白激酶（MAPK）信号在肺上皮细胞EMT相关变化中的作用和机制。将肺上皮1HAEo−细胞暴露于TGF-β1导致96小时内EMT的形态学和分子学变化;细胞-细胞接触丧失、细胞伸长、E-钙粘蛋白下调、纤连蛋白上调和I型胶原上调。TGF-β1可激活Smad 2/3和p38 MAPK信号通路。然而，Smad 2/3和p38 MAPK都不是E-cadherin下调所必需的，而p38 MAPK与纤连蛋白上调相关。Smad 2/3和p38 MAPK均参与TGF-β1诱导的胶原表达的调节。此外，这些数据表明，Smads和p38 MAPK差异调节肺上皮细胞EMT相关的变化。
Idiopathic pulmonary fibrosis is characterized by myofibroblast accumulation, extracellular matrix (ECM) remodeling and excessive collagen deposition. ECM-producing myofibroblasts may originate from epithelial cells through epithelial to mesenchymal transition (EMT). TGF-β1 is an inducer of EMT in pulmonary epithelial cells in vitro and in vivo, though the mechanisms are unclear. We hypothesized that TGF-β1 induced EMT through Smad dependent and independent processes. To test this hypothesis, we studied the roles and mechanisms of TGF-β1 induced Smad and p38 Mitogen Activated Protein Kinase (MAPK) signaling in EMT-related changes in pulmonary epithelial cells. Exposure of pulmonary epithelial 1HAEo− cells to TGF-β1 resulted in morphological and molecular changes of EMT over a 96-hour period; loss of cell-cell contact, cell elongation, down-regulation of E-cadherin, up-regulation of fibronectin, and up-regulation of collagen I. Both Smad2/3 and p38 MAPK signaling pathways were activated by TGF-β1. However, neither Smad2/3 nor p38 MAPK were required for the down-regulation of E-cadherin, yet p38 MAPK was associated with fibronectin up-regulation. Both Smad2/3 and p38 MAPK had a role in regulation of TGF-β1 induced collagen expression. Furthermore, these data demonstrate that Smads and p38 MAPK differentially regulate EMT-related changes in pulmonary epithelial cells.
登录
查看更多内容
影响因子：
6
作者：
Saika, S;Kono-Saika, S;Roberts, AB
通讯作者：
Roberts, AB
影响因子：
7.5
作者：
Kadler KE;Hill A;Canty-Laird EG
通讯作者：
Canty-Laird EG
影响因子：
4.4
作者：
Bonniaud, P;Kolb, M;Gauldie, J
通讯作者：
Gauldie, J
影响因子：
4.1
作者：
Phanish, MK;Wahab, NA;Dockrell, MEC
通讯作者：
Dockrell, MEC
DOI：
10.1152/ajplung.00187.2001
发表时间：
2002-07-01
影响因子：
4.9
作者：
Matsuoka, H;Arai, T;Hayashi, S
通讯作者：
Hayashi, S