Roles of p38 MAPK and JNK in TGF-β1-induced Human Alveolar Epithelial to Mesenchymal Transition
Roles of p38 MAPK and JNK in TGF-β1-induced Human Alveolar Epithelial to Mesenchymal Transition
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DOI：
10.1016/j.arcmed.2013.01.004
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发表时间：
2013-02-01
影响因子：
7.7
通讯作者：
Yang, Jiong
中科院分区：
文献类型：
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作者：
Chen, Hai-hua;Zhou, Xian-long;Yang, Jiong
背景与目的。尽管进行了积极的治疗，特发性肺纤维化（IPF）仍具有较高的发病率和死亡率。本研究的目的是探讨p38丝裂原活化蛋白激酶（MAPK）和c - Jun氨基末端激酶（JNK）在转化生长因子 - β1（TGF - β1）诱导的人肺泡上皮 - 间质转化（EMT）中的作用，这可能是IPF的一种潜在机制。
方法。用TGF - β1（3 ng/mL）处理A549细胞48小时以诱导EMT。通过蛋白质印迹法检测间充质表型标志物包括结蛋白、α - 平滑肌肌动蛋白（α - SMA）和波形蛋白的表达，以及上皮表型标志物包括E - 钙黏蛋白、紧密连接蛋白 - 1（ZO - 1）和水通道蛋白 - 5（AQP5）的表达。利用基因沉默以及抑制剂SB - 203580和SP - 600125研究p38 MAPK和JNK在TGF - β1介导的EMT中的作用。
结果。数据显示，TGF - β1诱导具有肺泡Ⅱ型上皮细胞表型的A549细胞发生EMT。EMT过程伴随着形态学改变以及肌成纤维细胞标志物结蛋白、α - SMA和波形蛋白的表达，同时上皮细胞标志物E - 钙黏蛋白、ZO - 1和AQP5下调。TGF - β1诱导的EMT通过p38 MAPK和JNK的磷酸化发生，并且可被抑制剂SB - 203580和SP - 600125以及基因沉默所抑制。
结论。TGF - β1部分通过p38 MAPK和JNK的激活诱导A549肺泡上皮细胞（AECs）发生EMT，这支持了肺上皮细胞中存在EMT的观点。（C）2013墨西哥国立医学与营养科学研究所。由爱思唯尔公司出版。
Background and Aims. Idiopathic pulmonary fibrosis (IPF) is associated with significant morbidity and mortality despite aggressive therapy. The aim of the present study is to investigate the roles of p38 MAPK and JNK in TGF-beta 1-induced human alveolar epithelial to mesenchymal transition (EMT), which could be a possible mechanism of IPF.Methods. A549 cells were treated with TGF-beta 1 (3 ng/mL) for 48 h to induce EMT. The expression of mesenchymal phenotypic markers including desmin, a-smooth muscle actin (alpha-SMA) and vimentin, and expression of epithelial phenotypic markers including E-cadherin, zonula occludens-1 (ZO-1) and aquaporin-5 (AQP5) were detected by Western blot. The roles of p38 MAPK and INK in TGF-beta 1-mediated EMT were investigated using gene silencing and inhibitor SB-203580 and SP-600125.Results. The data showed that TGF-beta 1 induced A549 cells with an alveolar epithelial type II cell phenotype to undergo EMT. The process of EMT was accompanied by morphological alteration and expression of the myofibroblast marker desmin, alpha-SMA and vimentin, concomitant with a downregulation of the epithelial cell marker E-cadherin, ZO-1 and AQP5. TGF-beta 1-induced EMT occurred through phosphorylation of p38 MAPK and JNK and was inhibited by inhibitor SB-203580 and SP-600125 and gene silencing.Conclusions. TGF-beta 1 induces A549 alveolar epithelial cells (AECs) to undergo EMT partially via p38 MAPK and JNK activation and supports the concept of EMT in lung epithelial cells. (C) 2013 IMSS. Published by Elsevier Inc.