Breviscapine Alleviates Transforming Growth Factor-β1-Induced Epithelial-Mesenchymal Transition of Human Alveolar Epithelium Cells A549 via Inhibiting PI3K/AKT/GSK3β Pathway

Xiaobo Ling

Article ID: 6895
Vol 36, Issue 3, 2022
DOI: https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.69
Received: 9 July 2022; Accepted: 9 July 2022; Available online: 9 July 2022; Issue release: 9 July 2022

Abstract

Background: Considering the crucial role epithelial-to-mesenchymal transition (EMT) plays to promote pulmonary fibrosis, it has hence become the objective to reveal the effects of breviscapine on EMT of transforming growth factor-β1 (TGF-β1)-induced human pulmonary fibrosis model. Methods: During the experiments, A549 cells were used to establish a cellular pulmonary fibrosis model in vitro, which were mimicked by TGF-β1 intervention and further treated with breviscapine, or the PI3K activator insulin-like growth factor-1 (IGF-1). The following assays, including MTT (viability), wound healing (migration) and Transwell (invasion) were carried out as appropriate. The morphology of pulmonary fibrosis cells was observed under the microscope. The expressions of EMT-, TGF-β1/Smad pathway-, and PI3K/AKT/GSK3β pathway-related proteins were quantified based on the tests of RT-qPCR and western blot as needed. Results: Corresponding, the results here highlighted that TGF-β1 down-regulated the level of E-cadherin and up-regulated those of N-cadherin and Fibronectin in A549 cells. Breviscapine abrogated the promoting effects of TGF-β1 on the malignant phenotypes of A549 cells and on EMT-related factors. However, IGF-1 offset the effects of breviscapine on regulating the migration, invasion, and the expression levels of factors related to EMT and TGF-β1/Smad pathway in A549 cells with the treatment of TGF-β1. Conclusions: Breviscapine has the suppressive effects on the proliferation, migration, invasion, EMT, and TGF-β1/Smad signaling of TGF-β1-treated pulmonary fibrotic cells in vitro by blocking PI3K/AKT/GSK3β pathway, and possesses great potential as a feasible candidate for pulmonary fibrosis.


Keywords

pulmonary fibrosis;breviscapine;transforming growth factor-β1;epithelial-to-mesenchymal transition


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