Ficolin-1 ameliorates pulmonary fibrosis via directly binding to TGF-β1
Abstract Background Ficolins were originally identified as proteins that bind to transforming growth factor-β1 (TGF-β1). They are capable of activating the complement system through lectin pathway for immune system protection. Ficolin-2 and 3 have been identified in patients with interstitial lung d...
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BMC
2024-11-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-024-05894-1 |
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| author | Pengfei Gao Yanjiao Lu Kun Tang Wei Wang Tongsheng Wang Yingwei Zhu Jianping Zhao Yimin Mao |
| author_facet | Pengfei Gao Yanjiao Lu Kun Tang Wei Wang Tongsheng Wang Yingwei Zhu Jianping Zhao Yimin Mao |
| author_sort | Pengfei Gao |
| collection | DOAJ |
| description | Abstract Background Ficolins were originally identified as proteins that bind to transforming growth factor-β1 (TGF-β1). They are capable of activating the complement system through lectin pathway for immune system protection. Ficolin-2 and 3 have been identified in patients with interstitial lung diseases (ILD) and their function in these diseases is currently being explored. In contrast, the functional role of ficolin-1 in pulmonary fibrosis is still elusive and remains to be elucidated. Methods The expression of ficolin-1 in the plasma of idiopathic pulmonary fibrosis (IPF) and connective tissue disease (CTD)-ILD patients was first determined. As the orthologue of human ficolin-1, ficolin-B knockout and ficolin-B overexpression were used to establish bleomycin (BLM)-induced pulmonary fibrosis mouse model. Co-immunoprecipitation, immunofluorescence and RNA sequencing were utilized to explore and expound on the expression and the functional mechanism of ficolin-1 in pulmonary fibrosis. Results Compared with healthy controls, plasma ficolin-1 was significantly decreased in patients with IPF and CTD-ILD. In the bleomycin (BLM)-induced mice model, ficolin-B deficiency aggravated lung injury and fibrosis. There was also observed increase in TGF-β1 levels and enhanced downstream signaling. However, the overexpression of ficolin-B showed preventative and therapeutic efficacy against lung fibrosis. Furthermore, coimmunoprecipitation studies revealed the direct interaction between ficolin-1 and TGF-β1 in human plasma, which was further confirmed by the colocalization of ficolin-1 and TGF-β1 in lung tissues. Conclusions Ficolin-1 inhibits pulmonary fibrosis by directly binding to the key profibrogenic factor TGF-β1, marking it as a potential target for therapy in the treatment of fibrotic lung diseases. |
| format | Article |
| id | doaj-art-8a3d8a2992884a85a70b898be6128f52 |
| institution | OA Journals |
| issn | 1479-5876 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-8a3d8a2992884a85a70b898be6128f522025-08-20T02:22:29ZengBMCJournal of Translational Medicine1479-58762024-11-0122111510.1186/s12967-024-05894-1Ficolin-1 ameliorates pulmonary fibrosis via directly binding to TGF-β1Pengfei Gao0Yanjiao Lu1Kun Tang2Wei Wang3Tongsheng Wang4Yingwei Zhu5Jianping Zhao6Yimin Mao7Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and TechnologyDepartment of Respiratory and Critical Care Medicine, Tongji Hospital of Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat- Sen UniversityDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and TechnologyDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and TechnologyDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and TechnologyDepartment of Respiratory and Critical Care Medicine, Tongji Hospital of Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and TechnologyAbstract Background Ficolins were originally identified as proteins that bind to transforming growth factor-β1 (TGF-β1). They are capable of activating the complement system through lectin pathway for immune system protection. Ficolin-2 and 3 have been identified in patients with interstitial lung diseases (ILD) and their function in these diseases is currently being explored. In contrast, the functional role of ficolin-1 in pulmonary fibrosis is still elusive and remains to be elucidated. Methods The expression of ficolin-1 in the plasma of idiopathic pulmonary fibrosis (IPF) and connective tissue disease (CTD)-ILD patients was first determined. As the orthologue of human ficolin-1, ficolin-B knockout and ficolin-B overexpression were used to establish bleomycin (BLM)-induced pulmonary fibrosis mouse model. Co-immunoprecipitation, immunofluorescence and RNA sequencing were utilized to explore and expound on the expression and the functional mechanism of ficolin-1 in pulmonary fibrosis. Results Compared with healthy controls, plasma ficolin-1 was significantly decreased in patients with IPF and CTD-ILD. In the bleomycin (BLM)-induced mice model, ficolin-B deficiency aggravated lung injury and fibrosis. There was also observed increase in TGF-β1 levels and enhanced downstream signaling. However, the overexpression of ficolin-B showed preventative and therapeutic efficacy against lung fibrosis. Furthermore, coimmunoprecipitation studies revealed the direct interaction between ficolin-1 and TGF-β1 in human plasma, which was further confirmed by the colocalization of ficolin-1 and TGF-β1 in lung tissues. Conclusions Ficolin-1 inhibits pulmonary fibrosis by directly binding to the key profibrogenic factor TGF-β1, marking it as a potential target for therapy in the treatment of fibrotic lung diseases.https://doi.org/10.1186/s12967-024-05894-1Pulmonary fibrosisBleomycinFicolin-1Ficolin-BTGF-β1 |
| spellingShingle | Pengfei Gao Yanjiao Lu Kun Tang Wei Wang Tongsheng Wang Yingwei Zhu Jianping Zhao Yimin Mao Ficolin-1 ameliorates pulmonary fibrosis via directly binding to TGF-β1 Journal of Translational Medicine Pulmonary fibrosis Bleomycin Ficolin-1 Ficolin-B TGF-β1 |
| title | Ficolin-1 ameliorates pulmonary fibrosis via directly binding to TGF-β1 |
| title_full | Ficolin-1 ameliorates pulmonary fibrosis via directly binding to TGF-β1 |
| title_fullStr | Ficolin-1 ameliorates pulmonary fibrosis via directly binding to TGF-β1 |
| title_full_unstemmed | Ficolin-1 ameliorates pulmonary fibrosis via directly binding to TGF-β1 |
| title_short | Ficolin-1 ameliorates pulmonary fibrosis via directly binding to TGF-β1 |
| title_sort | ficolin 1 ameliorates pulmonary fibrosis via directly binding to tgf β1 |
| topic | Pulmonary fibrosis Bleomycin Ficolin-1 Ficolin-B TGF-β1 |
| url | https://doi.org/10.1186/s12967-024-05894-1 |
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