CD109 Attenuates Bleomycin-induced Pulmonary Fibrosis by Inhibiting TGF-β Signaling

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.