Chen Qin, Liao Xing, Lin Ling, Wu Ling, Tang Qiuyu
Department of Pediatrics, Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian 350000, P.R. China.
Exp Ther Med. 2023 Jan 20;25(3):103. doi: 10.3892/etm.2023.11802. eCollection 2023 Mar.
Forkhead box F1 (FOXF1) has been reported to be associated with lung development. However, the role of FOXF1 in asthma is still not fully understood. In the present study, the biological role and the potential mechanism of FOXF1 was explored in transforming growth factor β1 (TGF-β1)-induced bronchial epithelial cell injury. Reverse transcription-quantitative PCR and western blotting were performed to detect the expression levels of FOXF1 and cadherin (CDH) 11 in TGF-β1-induced bronchial epithelial cells. Proliferation, apoptosis and inflammation were assessed using Cell Counting Kit-8 assay, flow cytometry, western blotting and ELISA. Fibrosis and epithelial-mesenchymal transition (EMT) were evaluated using immunofluorescence and western blotting. The expression levels of the proteins involved in the Wnt/β-catenin pathway were detected by western blotting. The results indicated that FOXF1 expression was downregulated, while CDH11 expression was upregulated in TGF-β1-treated BEAS-2B cells. FOXF1 overexpression promoted proliferation, inhibited induction of apoptosis and suppressed the inflammatory response of BEAS-2B cells exposed to TGF-β1. In addition, FOXF1 overexpression restrained TGF-β1-induced bronchial epithelial fibrosis and EMT and inhibited the activation of the Wnt/β-catenin pathway. CDH11 overexpression reversed the effects of FOXF1 overexpression on proliferation, apoptosis, fibrosis, EMT and inflammation by regulating the Wnt/β-catenin pathway. Collectively, the results of the present study suggested that FOXF1 regulated TGF-β1-induced BEAS-2B cell injury by inhibiting CDH11-mediated Wnt/β-catenin signaling. This may provide a novel therapeutic strategy for the treatment of asthma.
据报道，叉头框蛋白F1（FOXF1）与肺发育有关。然而，FOXF1在哮喘中的作用仍未完全明确。在本研究中，探讨了FOXF1在转化生长因子β1（TGF-β1）诱导的支气管上皮细胞损伤中的生物学作用及潜在机制。采用逆转录定量PCR和蛋白质印迹法检测TGF-β1诱导的支气管上皮细胞中FOXF1和钙黏蛋白（CDH）11的表达水平。使用细胞计数试剂盒-8法、流式细胞术、蛋白质印迹法和酶联免疫吸附测定法评估细胞增殖、凋亡和炎症反应。采用免疫荧光法和蛋白质印迹法评估纤维化和上皮-间质转化（EMT）。通过蛋白质印迹法检测Wnt/β-连环蛋白信号通路相关蛋白的表达水平。结果表明，在TGF-β1处理的BEAS-2B细胞中，FOXF1表达下调，而CDH11表达上调。FOXF1过表达促进了细胞增殖，抑制了TGF-β1诱导的BEAS-2B细胞凋亡，并抑制了炎症反应。此外，FOXF1过表达抑制了TGF-β1诱导的支气管上皮纤维化和EMT，并抑制了Wnt/β-连环蛋白信号通路的激活。CDH11过表达通过调节Wnt/β-连环蛋白信号通路逆转了FOXF1过表达对细胞增殖、凋亡、纤维化、EMT和炎症的影响。本研究结果表明，FOXF1通过抑制CDH11介导的Wnt/β-连环蛋白信号传导来调节TGF-β1诱导的BEAS-2B细胞损伤。这可能为哮喘治疗提供一种新的治疗策略。
