Journal Article

Ficolin-1 ameliorates pulmonary fibrosis via directly binding to TGF-β1

Gao, Pengfei, Wang, Wei, Wang, Tongsheng, Tang, Kun, Lu, Yanjiao, Zhao, Jianping, Zhu, Yingwei, Mao, Yimin

2024

Overview

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.

• Publisher: BioMed Central,BMC
• Subject: Animals / Biomedical and Life Sciences / Biomedicine / Bleomycin / Disease Models, Animal / Female / Fibrosis / Ficolin-1 / Ficolin-B / Ficolins / Humans / Idiopathic Pulmonary Fibrosis - metabolism / Idiopathic Pulmonary Fibrosis - pathology / Lectins - metabolism / Lung - metabolism / Lung - pathology / Male / Medicine/Public Health / Mice / Mice, Inbred C57BL / Mice, Knockout / Middle Aged / Protein Binding / Pulmonary fibrosis / Pulmonary Fibrosis - metabolism / Pulmonary Fibrosis - pathology / Signal Transduction / TGF-β1 / Transforming Growth Factor beta1 - metabolism