Secretoglobin 3A2 suppresses bleomycin-induced pulmonary fibrosis by transforming growth factor beta signaling down-regulation
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Updated: Jun 2, 2026
Oropharyngeal Administration of Bleomycin in the Murine Model of Pulmonary Fibrosis
Published on: May 9, 2025
Reiko Kurotani1, Satoshi Okumura, Tsutomu Matsubara
1Laboratory of Metabolism, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA.
Abstract:
With increasing worldwide rates of morbidity and mortality of pulmonary fibrosis, the development of effective therapeutics for this disease is of great interest. Secretoglobin (SCGB) 3A2, a novel cytokine-like molecule predominantly expressed in pulmonary airways epithelium, exhibits anti-inflammatory and growth factor activities. In the current study SCGB3A2 was found to inhibit TGFβ-induced differentiation of fibroblasts to myofibroblasts, a hallmark of the fibrogenic process, using pulmonary fibroblasts isolated from adult mice. This induction was through increased phosphorylation of STAT1 and expression of SMAD7 and decreased phosphorylation of SMAD2 and SMAD3. To demonstrate the effect of SCGB3A2 on the TGFβ signaling in vivo, a bleomycin-induced pulmonary fibrosis mouse model was used. Mice were administered bleomycin intratracheally followed by intravenous injection of recombinant SCGB3A2. Histological examination in conjunction with inflammatory cell counts in bronchoalveolar lavage fluids demonstrated that SCGB3A2 suppressed bleomycin-induced pulmonary fibrosis. Microarray analysis was carried out using RNAs from lungs of bleomycin-treated mice with or without SCGB3A2 and normal mice treated with SCGB3A2. The results demonstrated that SCGB3A2 affects TGFβ signaling and reduces the expression of genes involved in fibrosis. This study suggests the potential utility of SCGB3A2 for targeting TGFβ signaling in the treatment of pulmonary fibrosis.
Insights
Secretoglobin (SCGB) 3A2 effectively inhibits pulmonary fibrosis by targeting TGFβ signaling pathways. This novel molecule shows promise as a therapeutic agent for treating lung fibrosis.
Area of Science:
- Pulmonary Medicine
- Molecular Biology
- Cell Biology
Background:
- Pulmonary fibrosis presents a growing global health challenge with limited effective treatments.
- Secretoglobin (SCGB) 3A2, an airway epithelium-expressed molecule, possesses anti-inflammatory and growth factor properties.
Purpose of the Study:
- To investigate the inhibitory effects of SCGB3A2 on fibroblast differentiation into myofibroblasts, a key process in pulmonary fibrosis.
- To evaluate the therapeutic potential of SCGB3A2 in a bleomycin-induced mouse model of pulmonary fibrosis.
Main Methods:
- In vitro studies using mouse pulmonary fibroblasts to assess SCGB3A2's impact on TGFβ signaling pathways (STAT1, SMAD7, SMAD2, SMAD3).
- In vivo studies utilizing a bleomycin-induced pulmonary fibrosis mouse model with SCGB3A2 administration.
- Histological analysis and bronchoalveolar lavage cell counts to evaluate fibrosis and inflammation.
- Microarray analysis of lung tissue to identify gene expression changes related to TGFβ signaling and fibrosis.
Main Results:
- SCGB3A2 inhibited TGFβ-induced fibroblast to myofibroblast differentiation in vitro by modulating STAT1, SMAD7, SMAD2, and SMAD3 phosphorylation.
- SCGB3A2 administration significantly suppressed bleomycin-induced pulmonary fibrosis in mice, reducing histological damage and inflammation.
- Microarray analysis confirmed that SCGB3A2 impacts TGFβ signaling and downregulates pro-fibrotic gene expression.
Conclusions:
- SCGB3A2 demonstrates potent anti-fibrotic effects by inhibiting key components of the TGFβ signaling pathway.
- SCGB3A2 holds significant potential as a therapeutic agent for pulmonary fibrosis.
- Targeting TGFβ signaling with SCGB3A2 represents a promising strategy for treating lung fibrosis.
