Related Experiment Video
Updated: Jul 4, 2025
Oropharyngeal Administration of Bleomycin in the Murine Model of Pulmonary Fibrosis
Published on: May 9, 2025
CD109 Attenuates Bleomycin-induced Pulmonary Fibrosis by Inhibiting TGF-β Signaling
Hyogo Naoi1, Yuzo Suzuki1, Asuka Miyagi2
1Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Abstract:
Pulmonary fibrosis is a fatal condition characterized by fibroblast and myofibroblast proliferation and collagen deposition. TGF-β plays a pivotal role in the development of pulmonary fibrosis. Therefore, modulation of TGF-β signaling is a promising therapeutic strategy for treating pulmonary fibrosis. To date, however, interventions targeting TGF-β have not shown consistent efficacy. CD109 is a GPI-anchored glycoprotein that binds to TGF-β receptor I and negatively regulates TGF-β signaling. However, no studies have examined the role and therapeutic potential of CD109 in pulmonary fibrosis. The purpose of this study was to determine the role and therapeutic value of CD109 in bleomycin-induced pulmonary fibrosis. CD109-transgenic mice overexpressing CD109 exhibited significantly attenuated pulmonary fibrosis, preserved lung function, and reduced lung fibroblasts and myofibroblasts compared with wild-type (WT) mice. CD109-/- mice exhibited pulmonary fibrosis comparable to WT mice. CD109 expression was induced in variety types of cells, including lung fibroblasts and macrophages, upon bleomycin exposure. Recombinant CD109 protein inhibited TGF-β signaling and significantly decreased ACTA2 expression in human fetal lung fibroblast cells in vitro. Administration of recombinant CD109 protein markedly reduced pulmonary fibrosis in bleomycin-treated WT mice in vivo. Our results suggest that CD109 is not essential for the development of pulmonary fibrosis, but excess CD109 protein can inhibit pulmonary fibrosis development, possibly through suppression of TGF-β signaling. CD109 is a novel therapeutic candidate for treating pulmonary fibrosis.
Insights
CD109 protein can inhibit pulmonary fibrosis, a fatal lung disease. Overexpressing CD109 in mice reduced fibrosis, suggesting CD109 is a potential therapeutic for pulmonary fibrosis.
Area of Science:
- Pulmonary Medicine
- Cell Biology
- Molecular Biology
Background:
- Pulmonary fibrosis is a fatal lung disease driven by fibroblast proliferation and collagen deposition.
- Transforming growth factor-beta (TGF-β) signaling is crucial in pulmonary fibrosis pathogenesis, but TGF-β-targeted therapies show inconsistent efficacy.
- CD109, a glycoprotein, negatively regulates TGF-β signaling, yet its role in pulmonary fibrosis remains unstudied.
Purpose of the Study:
- To investigate the role and therapeutic potential of CD109 in bleomycin-induced pulmonary fibrosis.
Main Methods:
- Evaluated pulmonary fibrosis in CD109-transgenic and CD109 knockout mice after bleomycin challenge.
- Assessed lung function, fibroblast/myofibroblast populations, and CD109 expression in response to bleomycin.
- Examined the in vitro effects of recombinant CD109 protein on TGF-β signaling and ACTA2 expression in human lung fibroblasts.
- Investigated the in vivo therapeutic efficacy of recombinant CD109 protein in bleomycin-treated mice.
Main Results:
- CD109 overexpression attenuated pulmonary fibrosis, preserved lung function, and reduced lung fibroblasts/myofibroblasts in mice.
- CD109 knockout mice showed pulmonary fibrosis levels comparable to wild-type mice.
- Recombinant CD109 protein inhibited TGF-β signaling and decreased ACTA2 expression in vitro.
- In vivo administration of recombinant CD109 protein significantly reduced bleomycin-induced pulmonary fibrosis.
Conclusions:
- CD109 is not essential for pulmonary fibrosis development but can inhibit its progression.
- Excess CD109 protein suppresses TGF-β signaling, offering a potential mechanism for its antifibrotic effects.
- CD109 represents a novel therapeutic candidate for treating pulmonary fibrosis.
