{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["14(8)"],"submitter":["Zhao L"],"funding":["National Key Research and Development Program of China Stem Cell and Translational Research","Guangdong Provincial Natural Science Foundation","National Natural Science Foundation of China"],"pubmed_abstract":["Pulmonary fibrosis poses a significant health threat with very limited therapeutic options available. In this study, we reported the enhanced expression of mesenchymal homobox 1 (MEOX1) in pulmonary fibrosis patients, especially in their fibroblasts and endothelial cells, and confirmed MEOX1 as a central orchestrator in the activation of profibrotic genes. By high-throughput screening, we identified Ailanthone (AIL) from a natural compound library as the first small molecule capable of directly targeting and suppressing MEOX1. AIL demonstrated the ability to inhibit both the activation of fibroblasts and endothelial-to-mesenchymal transition of endothelial cells when challenged by transforming growth factor-<i>β</i>1 (TGF-<i>β</i>1). In an animal model of bleomycin-induced pulmonary fibrosis, AIL effectively mitigated the fibrotic process and restored respiratory functions. Mechanistically, AIL acted as a suppressor of MEOX1 by disrupting the interaction between the transcription factor JUN and the promoter of MEOX1, thereby inhibiting MEOX1 expression and activity. In summary, our findings pinpointed MEOX1 as a cell-specific and clinically translatable target in fibrosis. Moreover, we demonstrated the potent anti-fibrotic effect of AIL in pulmonary fibrosis, specifically through the suppression of JUN-dependent MEOX1 activation."],"journal":["Acta pharmaceutica Sinica. B"],"pagination":["3543-3560"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11365432"],"repository":["biostudies-literature"],"pubmed_title":["Ailanthone ameliorates pulmonary fibrosis by suppressing JUN-dependent MEOX1 activation."],"pmcid":["PMC11365432"],"pubmed_authors":["Wu J","Zhu Y","Qin J","Tao H","Lin Y","Cai B","Zhao L","Yin F","Huang Y","Shen A","Zhang Y","Liang L","Chen X","Yu XY"],"additional_accession":[]},"is_claimable":false,"name":"Ailanthone ameliorates pulmonary fibrosis by suppressing JUN-dependent MEOX1 activation.","description":"Pulmonary fibrosis poses a significant health threat with very limited therapeutic options available. In this study, we reported the enhanced expression of mesenchymal homobox 1 (MEOX1) in pulmonary fibrosis patients, especially in their fibroblasts and endothelial cells, and confirmed MEOX1 as a central orchestrator in the activation of profibrotic genes. By high-throughput screening, we identified Ailanthone (AIL) from a natural compound library as the first small molecule capable of directly targeting and suppressing MEOX1. AIL demonstrated the ability to inhibit both the activation of fibroblasts and endothelial-to-mesenchymal transition of endothelial cells when challenged by transforming growth factor-<i>β</i>1 (TGF-<i>β</i>1). In an animal model of bleomycin-induced pulmonary fibrosis, AIL effectively mitigated the fibrotic process and restored respiratory functions. Mechanistically, AIL acted as a suppressor of MEOX1 by disrupting the interaction between the transcription factor JUN and the promoter of MEOX1, thereby inhibiting MEOX1 expression and activity. In summary, our findings pinpointed MEOX1 as a cell-specific and clinically translatable target in fibrosis. Moreover, we demonstrated the potent anti-fibrotic effect of AIL in pulmonary fibrosis, specifically through the suppression of JUN-dependent MEOX1 activation.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Aug","modification":"2026-06-03T00:24:50.059Z","creation":"2024-11-15T04:46:12.798Z"},"accession":"S-EPMC11365432","cross_references":{"pubmed":["39220862"],"doi":["10.1016/j.apsb.2024.04.013"]}}