Fibroblast Growth Factor 2 Augments Transforming Growth Factor Beta 1 Induced Epithelial-mesenchymal Transition in Lung Cell Culture Model.
Fibroblast Growth Factor 2 Augments Transforming Growth Factor Beta 1 Induced Epithelial-mesenchymal Transition in Lung Cell Culture Model.
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DOI：
10.18502/ijaai.v19i4.4110
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发表时间：
2020-08-25
期刊：
影响因子：
--
通讯作者：
Salem ML
中科院分区：
文献类型：
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作者：
El-Baz LMF;Shoukry NM;Hafez HS;Guzy RD;Salem ML
损伤后肺上皮细胞再生受损可能有助于肺纤维化的发展。上皮-间质转化（EMT）是胚胎发育、损伤后伤口愈合甚至癌症进展中的关键事件。以往的研究表明，转化生长因子β 1（TGFβ1）和成纤维细胞生长因子2（FGF 2）的组合在癌症转移过程中诱导EMT。然而，这种协同作用在诱导与损伤后伤口愈合相关的EMT方面仍有待阐明。本研究旨在确定FGF 2对TGFβ1诱导的人肺上皮细胞EMT的影响。BEAS-2B和A549细胞用TGFβ1、FGF 2或两者处理。EMT表型进行了形态学研究，并通过测量mRNA的表达水平，使用实时定量PCR。免疫印迹和免疫荧光染色检测E-cadherin的表达。使用伤口愈合测定确认细胞迁移。TGFβ1可诱导BEAS-2B细胞形态学改变和细胞迁移能力显著增加。TGFβ1显著降低E-钙粘蛋白（CDH 1）mRNA表达，显著诱导N-钙粘蛋白（CDH 2）、腱生蛋白C（TNC）、纤维连接蛋白（FN）、肌动蛋白α 2（ACTA 2）和COL 1A 1的表达。虽然单独的FGF 2没有显著改变EMT基因表达，但它增强了TGFβ1诱导的对CDH 1的抑制和对ACTA 2的上调，但对TNC、FN和CDH 2没有影响。FGF 2显著抑制TGFβ1诱导的COL 1A 1表达。此外，FGF 2还能维持TGFβ1诱导的细胞形态学改变，并促进TGFβ1处理的细胞迁移。本研究提示TGFβ1和FGF 2在诱导肺上皮细胞EMT中具有协同作用，可能在创伤愈合和损伤后组织修复中发挥重要作用。
Impaired lung epithelial cell regeneration following injury may contribute to the development of pulmonary fibrosis. Epithelial-mesenchymal transition (EMT) is a critical event in embryonic development, wound healing following injury, and even cancer progression. Previous studies have shown that the combination of transforming growth factor beta-1 (TGFβ1) and fibroblast growth factor 2 (FGF2) induces EMT during cancer metastasis. However, this synergy remains to be elucidated in inducing EMT associated with wound healing after injury. We set out this study to determine the effect of FGF2 on TGFβ1-induced EMT in human lung epithelium. BEAS-2B and A549 cells were treated with TGFβ1, FGF2 or both. EMT phenotype was investigated morphologically and by measuring mRNA expression levels using quantitative real-time PCR. E-cadherin expression was assayed by western blot and immunofluorescence staining. Cell migration was confirmed using a wound-healing assay. TGFβ1 induced a morphological change and a significant increase in cell migration of BEAS-2B cells. TGFβ1 significantly reduced E-cadherin (CDH1) mRNA expression and markedly induced expression of N-cadherin (CDH2), tenascin C (TNC), fibronectin (FN), actin alpha 2 (ACTA2) and COL1A1. While FGF2 alone did not significantly alter EMT gene expression, it enhanced TGFβ1-induced suppression of CDH1 and upregulation of ACTA2, but not TNC, FN and CDH2. FGF2 significantly inhibited TGFβ1-induced COL1A1 expression. Furthermore, FGF2 maintained TGFβ1-induced morphologic changes and increased the migration of TGFβ1-treated cells. This study suggests a synergistic effect between TGFβ1 and FGF2 in inducing EMT in lung epithelial cells, which may play an important role in wound healing and tissue repair after injury.