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Updated: Apr 12, 2026
A Mouse Model of Pulmonary Fibrosis Induced by Nasal Bleomycin Nebulization
Published on: January 20, 2023
Angiotensin-Converting Enzyme 2 Attenuates Bleomycin-Induced Lung Fibrosis in Mice
Background:
Local renin-angiotensin system (RAS) activation has been shown to play an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). It has been reported that angiotensin-converting enzyme 2 (ACE2) could inhibit RAS-mediated epithelial injury and fibrogenesis and that ACE2 deficiency could aggravate acute and chronic lung injury. Through research, it could be deduced that ACE2 could protect against pulmonary fibrosis as a therapeutic target.
Methods:
Time-course analysis of the pathological characteristics of bleomycin-induced lung fibrosis was undertaken in a mouse model, and the effect of exogenous ACE2 on lung fibrosis was studied. Immunohistchemistry (IHC) staining and western blot (WB) testing for AGT and ACE2 were performed to evaluate the regulation of local RAS. TUNEL staining was used to observe epithelial apoptosis. Leukocyte common antigen (LCA) and pulmonary surfactant-associated protein A (SP-A) IHC staining and WB testing were performed to assess the inflammatory response and epithelial regeneration. Masson's staining and a hydroxyproline assay were performed to examine collagen deposition. IHC staining and WB testing for TGF-β1 and α-SMA were performed to investigate the regulation of pro-fibrotic cytokines and the activation of fibroblasts.
Results:
Exogenous ACE2 attenuated bleomycin-induced lung fibrosis by reversing the reduction of local ACE2 and by suppressing the elevation of AGT. ACE2 decreased the apoptosis index and LCA levels and ameliorated the dynamic change in SP-A level, thus protecting against epithelial injury. Reductions of TGF-β1 and α-SMA were also found in ACE2-treated mice, indicating the inhibition of fibrogenesis.
Conclusion:
ACE2 attenuated bleomycin-induced lung fibrosis as an anti-inflammatory anti-apoptotic and anti-fibrotic agent, and it might be a promising therapeutic target for IPF.
Insights
Angiotensin-converting enzyme 2 (ACE2) demonstrated anti-inflammatory, anti-apoptotic, and anti-fibrotic effects, significantly reducing lung fibrosis in a mouse model. This suggests ACE2 is a potential therapeutic target for idiopathic pulmonary fibrosis (IPF).
Area of Science:
- Pulmonary Medicine
- Renal Physiology
- Cellular Biology
Background:
- Local renin-angiotensin system (RAS) activation is implicated in idiopathic pulmonary fibrosis (IPF) pathogenesis.
- Angiotensin-converting enzyme 2 (ACE2) may inhibit RAS-mediated epithelial injury and fibrogenesis.
- ACE2 deficiency exacerbates acute and chronic lung injury, suggesting a protective role.
Purpose of the Study:
- To investigate the protective effect of ACE2 against pulmonary fibrosis.
- To evaluate ACE2 as a potential therapeutic target for IPF.
Main Methods:
- Time-course analysis of bleomycin-induced lung fibrosis in a mouse model.
- Assessment of exogenous ACE2 effects on lung fibrosis markers, including RAS components (AGT, ACE2), epithelial injury (apoptosis, SP-A), inflammation (LCA), collagen deposition, and fibrogenesis (TGF-β1, α-SMA).
- Utilized immunohistochemistry (IHC) and western blot (WB) for protein analysis, TUNEL staining for apoptosis, and Masson's staining/hydroxyproline assay for collagen.
Main Results:
- Exogenous ACE2 attenuated bleomycin-induced lung fibrosis by normalizing local ACE2 and suppressing AGT elevation.
- ACE2 treatment reduced epithelial apoptosis and inflammation, while improving epithelial regeneration markers.
- Fibrosis markers, including TGF-β1 and α-SMA, were significantly reduced in ACE2-treated mice.
Conclusions:
- ACE2 acts as an anti-inflammatory, anti-apoptotic, and anti-fibrotic agent, mitigating lung fibrosis.
- ACE2 demonstrates potential as a therapeutic target for idiopathic pulmonary fibrosis (IPF).
