Platyconic acid A‑induced PPM1A upregulation inhibits the proliferation, inflammation and extracellular matrix deposition of TGF‑β1‑induced lung fibroblasts

Su,Chengcheng; Tang,Yanfen; Wang,Cong; Huang,Haifeng; Hou,Haihui

doi:10.3892/mmr.2022.12845

Platyconic acid A‑induced PPM1A upregulation inhibits the proliferation, inflammation and extracellular matrix deposition of TGF‑β1‑induced lung fibroblasts

Authors:
- Chengcheng Su
- Yanfen Tang
- Cong Wang
- Haifeng Huang
- Haihui Hou
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Affiliations: Pneumology Department, Nantong Hospital of Traditional Chinese Medicine, Nantong Affiliated Hospital of Nanjing University of Chinese Medicine, Nantong, Jiangsu 226500, P.R. China
Published online on: September 6, 2022 https://doi.org/10.3892/mmr.2022.12845
Article Number: 329
Copyright: © Su et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Platyconic acid A (PA), the active component of Platycodi radix‑derived saponin, exerts ameliorating effects on liver fibrosis. Platycodon grandiflorum is used to treat lung disease. Therefore, the present study evaluated the effects of PA on pulmonary fibrosis. Transforming growth factor‑β1 (TGF‑β1) was used to induce MRC‑5 cells to establish an in vitro pulmonary fibrosis model. The viability of MRC‑5 cells in the presence or absence of TGF‑β1 induction was examined using a Cell Counting Kit‑8 assay and the results demonstrated that PA markedly decreased viability of TGF‑β1‑induced MRC‑5 cells in a dose‑dependent manner. Wound healing analysis, immunofluorescent staining and western blotting were performed to determine the levels of cell migration and expression of α‑smooth muscle actin and extracellular matrix (ECM)‑associated proteins. The results of the present study demonstrated that PA significantly suppressed the migration and ECM deposition of TGF‑β1‑induced MRC‑5 cells. Furthermore, results obtained from ELISA and western blotting demonstrated that PA exerted suppressive effects on the inflammation of MRC‑5 cells following TGF‑β1 stimulation. The mRNA and protein expression levels of protein phosphatase Mg2⁺/Mn2⁺‑dependent 1A (PPM1A) before and after transfection were assessed using reverse transcription‑quantitative PCR and western blotting and the results demonstrated that the mRNA and protein expression levels of PPM1A were significantly decreased following transfection with small interfering RNA targeting PPM1A. Moreover, following PPM1A knockdown, PA significantly inhibited the proliferation, migration, inflammation and ECM deposition of TGF‑β1‑induced MRC‑5 cells via activation of the SMAD/β‑catenin signaling pathway. In conclusion, PA activated PPM1A to ameliorate TGF‑β1‑elicited lung fibroblast injury via modulating SMAD/β‑catenin signaling.

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