Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by lung inflammation and excessive deposition of extracellular matrix components. Transforming growth factor-β1 (TGF-β1) induced epithelial–mesenchymal transformation of type 2 lung epithelial cells leads to excessive extracellular matrix deposition, which plays an important role in fibrosis. Our objective was to evaluate the effects of 3-cyclopropylmethoxy-4-(difluoromethoxy) benzoic acid (DGM) on pulmonary fibrosis and aimed to determine whether EMT plays a key role in the pathogenesis of pulmonary fibrosis and whether EMT can be used as a therapeutic target for DGM therapy to reduce IPF. Firstly, stimulation of in vitro cultured A549 cells to construct EMTs with TGF-β1. DGM treatment inhibited the expression of proteins such as α-SMA, vimentin, and collagen Ⅰ and increased the expression of E-cadherin. Accordingly, Smad2/3 phosphorylation levels were significantly reduced by DGM treatment. Secondly, models of tracheal instillation of bleomycin and DGM were used to treat rats to demonstrate their therapeutic effects, such as improving lung function, reducing lung inflammation and fibrosis, reducing collagen deposition, and reducing the expression of E-cadherin. In conclusion, DGM attenuates TGF-β1-induced EMT in A549 cells and bleomycin-induced pulmonary fibrosis in rats.

中文翻译：

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3-环丙基甲氧基-4-（二氟甲氧基）苯甲酸对 TGF-β1 诱导的体外上皮间质转化和体内博来霉素诱导的肺纤维化的抑制作用

特发性肺纤维化（IPF）是一种以肺部炎症和细胞外基质成分过度沉积为特征的进行性肺部疾病。转化生长因子-β1 (TGF-β1) 诱导 2 型肺上皮细胞的上皮-间质转化导致细胞外基质过度沉积，这在纤维化中起重要作用。我们的目的是评估 3-环丙基甲氧基-4-（二氟甲氧基）苯甲酸 (DGM) 对肺纤维化的影响，旨在确定 EMT 是否在肺纤维化的发病机制中起关键作用，以及 EMT 是否可用作治疗药物DGM 治疗的目标是降低 IPF。首先，用TGF-β1刺激体外培养的A549细胞构建EMTs。DGM 处理抑制了 α-SMA、波形蛋白等蛋白质的表达，和Ⅰ型胶原并增加E-钙粘蛋白的表达。因此，DGM 处理显着降低了 Smad2/3 磷酸化水平。其次，通过气管滴注博来霉素和DGM模型对大鼠进行治疗，证明其改善肺功能、减轻肺部炎症和纤维化、减少胶原沉积、降低E-cadherin表达等治疗效果。总之，DGM 减弱了 A549 细胞中 TGF-β1 诱导的 EMT 和大鼠中博来霉素诱导的肺纤维化。减少肺部炎症和纤维化，减少胶原蛋白沉积，减少 E-cadherin 的表达。总之，DGM 减弱了 A549 细胞中 TGF-β1 诱导的 EMT 和大鼠中博来霉素诱导的肺纤维化。减少肺部炎症和纤维化，减少胶原蛋白沉积，减少 E-cadherin 的表达。总之，DGM 减弱了 A549 细胞中 TGF-β1 诱导的 EMT 和大鼠中博来霉素诱导的肺纤维化。