FOXO4-D-Retro-Inverso targets extracellular matrix production and ameliorates pulmonary fibrosis
Objective:To investigate the effect of FOXO4 D-Retro-Inverso(FOXO4-DRI)on pulmonary fi-brosis of mice,fibroblast activation,and extracellular matrix(ECM)production.Methods:C57BL/6J male mice received intratracheal injection with bleomycin to induce pulmonary fibrosis,then treated with FOXO4-DRI,and lung tissues were obtained after 21 days.Lung structural changes and the expression of pulmonary fibrosis markers were observed.MRC5 was stimulated with TGF-β1 followed by FOXO4-DRI intervention,and then fibroblast activation markers and ECM proteins were detected.Results:Bleomycin-induced mice showed obvious structural changes,higher fibrosis scores(P<0.01),and elevated expression of pulmonary fibrosis markers(P<0.01).While FOXO4-DRI-treated mice showed alleviative structural changes and lower fibrosis scores(P<0.01),and lower expression of pulmonary fibrosis markers(P<0.01).TGF-β1 induced fibroblast activation and increased the level of ECM proteins(P<0.01),which was alleviated by FOXO4-DRI interven-tion(P<0.01).Conclusion:FOXO4-DRI inhibits the activation of lung fibroblasts and production of ECM proteins,thereby ameliorates lung fibrosis in mice.
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