Role of macrophage-to-myofibroblast transition in early pulmonary fibrosis induced by acute lung injury

HU Shengjuan; HU Die; WU Lei

doi:10.3969/j.issn.1002-266X.2025.09.008

Abstract：Objective To investigate the mechanism of action of macrophage-to-myofibroblast transition(MMT)on early pulmonary fibrosis induced by acute lung injury.Methods Eighteen SPF healthy mice were divided into the model group and control group.Mice in the model group were treated by lipopolysaccharide(LPS)to establish the early pulmo-nary fibrosis models,while mice in the control group received tracheal and intraperitoneal injections of equal volume of nor-mal saline at the same time points.On day 3,7,and 10 after modeling,lung tissue samples were collected from the mice.The extent of pulmonary fibrosis was assessed using the Ashcroft score.The number of myofibroblasts exhibiting MMT phe-notype[co-labeled with CD68 and α-smooth muscle actin(α-SMA)]in the lung tissues was measured by immunofluores-cence staining.The protein levels of mothers against decapentaplegic homolog 3(Smad3)and transforming growth factor-β1(TGF-β1)in the mouse lung tissues were detected by Western blotting and ELISA,respectively.Results Compared with the control group,the Ashcroft score significantly increased in the model group on day 7 and 10(all P<0.05).The relative protein expression levels of Smad3 and TGF-β1 in the lung tissues of the model group were significantly higher than those in the control group on day 7 and 10 after modeling(all P<0.05).In vitro,the protein expression levels of Smad3 and α-SMA,and the mRNA expression levels of α-SMA,Fibronectin,and Collagen-I in the intervention group in-creased significantly over time(all P<0.05).Conclusions As the duration of injury increases,the proportion of MMT-phenotype cells in the lung tissues of mice with acute lung injury gradually increases.MMT-phenotype cells may contrib-ute to the development and progression of pulmonary fibrosis in injured mice by regulating the TGF-β1/Smad3 signaling pathway.