Yifei Decoction Regulates the NGF/TRKA/PI3K/AKT Signaling Axis to Inhibit the Epithelial-Mesenchymal Transformation and Proliferation of Pulmonary Epithelial Cells in Bleomycin-Induced Pulmonary Fibrogenesis.

Abstract

BACKGROUND: It was important to find better therapeutic drugs for idiopathic pulmonary fibrosis (IPF), and in our previous study, Yifei decoction (YFT) alleviated IPF. A deeper understanding of its mechanisms of action could aid in the development of novel treatment strategies. METHODS: We established an IPF mouse model by administering bleomycin (BLM), followed by treatment with YFT. Histopathological analysis of lung tissue was conducted to evaluate the effects of YFT, along with transcriptomic profiling to identify key regulatory molecules involved in its therapeutic action. Immunofluorescence staining was performed for TRKA and surfactant protein C (SP-C) in IPF lung slices. A549 cells were induced with TGF-β1 to assess the effect of YFT on alveolar epithelial cells, and cells overexpressing TRKA were constructed. Western blotting analysis was performed to detect EMT- and PI3K/AKT pathway-related protein levels, and an EdU proliferation assay was conducted to measure the proliferation of A549 cells. RESULTS: YFT intervention reduced pathological lung injury in BLM-treated mice. GO enrichment analysis revealed enrichment of DEGs in the extracellular matrix and proteinaceous extracellular matrix. Analysis of the enriched KEGG pathways revealed enrichment of the PI3K-AKT signaling pathway. YFT also decreased the number of SP-C/TRKAcells in lung tissues, inhibited the expression of TRKA, and reduced the NGF concentration in TGF-β1-stimulated A549 cells. YFT reduced TRKA, PI3K, and AKT phosphorylation levels, EMT, and cell proliferation. However, these effects were eliminated when TRKA was overexpressed. CONCLUSION: YFT might regulate the NGF/TRKA/PI3K/AKT pathway to alleviate pulmonary fibrosis by reducing EMT and cell proliferation. This study laid the groundwork for future research on the possible enhancement of the therapeutic effect of YFT when YFT is combined with other medications.