Department of Medicine, Section of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, Illinois, USA AND Department of Zoology, Faculty of Science, Suez University, Suez, Egypt.
Department of Zoology, Faculty of Science, Suez University, Suez, Egypt.
Iran J Allergy Asthma Immunol. 2020 Aug 25;19(4):348-361. doi: 10.18502/ijaai.v19i4.4110.
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 fibroblast growth factor 2 (FGF2) on TGFβ1-induced EMT in the 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 collagen I (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.
肺上皮细胞损伤后的再生受损可能导致肺纤维化的发展。上皮-间充质转化 (EMT) 是胚胎发育、损伤后愈合以及甚至癌症进展中的一个关键事件。先前的研究表明，转化生长因子β-1 (TGFβ1) 和成纤维细胞生长因子 2 (FGF2) 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损伤后愈合相关的 EMT 中仍有待阐明。我们着手进行这项研究，以确定成纤维细胞生长因子 2 (FGF2) 对人肺上皮细胞中 TGFβ1 诱导的 EMT 的影响。BEAS-2B 和 A549 细胞用 TGFβ1、FGF2 或两者处理。通过测量 mRNA 表达水平从形态和形态上研究 EMT 表型；使用定量实时 PCR。通过 Western blot 和免疫荧光染色测定 E-钙粘蛋白表达。通过划痕愈合试验证实细胞迁移。TGFβ1 诱导 BEAS-2B 细胞形态发生变化和细胞迁移显著增加。TGFβ1 显著降低 E-钙粘蛋白 (CDH1) mRNA 表达并显著诱导 N-钙粘蛋白 (CDH2)、腱蛋白 C (TNC)、纤连蛋白 (FN)、肌动蛋白 α 2 (ACTA2) 和胶原蛋白 I (COL1A1) 的表达。虽然 FGF2 单独使用不会显著改变 EMT 基因表达，但它增强了 TGFβ1 诱导的 CDH1 抑制和 ACTA2 的上调，但不增强 TNC、FN 和 CDH2。FGF2 显著抑制 TGFβ1 诱导的 COL1A1 表达。此外，FGF2 维持 TGFβ1 诱导的形态变化并增加 TGFβ1 处理细胞的迁移。这项研究表明 TGFβ1 和 FGF2 之间在诱导肺上皮细胞 EMT 中具有协同作用，这可能在损伤后愈合和组织修复中起重要作用。
