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Updated: Aug 11, 2026
Oropharyngeal Administration of Bleomycin in the Murine Model of Pulmonary Fibrosis
Published on: May 9, 2025
Macrophage metalloelastase (MMP-12) deficiency does not alter bleomycin-induced pulmonary fibrosis in mice
Boris Manoury1, Soazig Nenan, Isabelle Guenon
1INSERM U620, Université de Rennes 1, Rennes, France. boris_manoury@hotmail.fr
Background:
Pulmonary fibrosis is characterized by excessive deposition of extracellular matrix in the interstitium resulting in respiratory failure. The role of remodeling mediators such as metalloproteinases (MMPs) and their inhibitors (TIMPs) in the fibrogenic process remains misunderstood. In particular, macrophage metalloelastase, also identified as MMP-12, is known to be involved in remodeling processes under pathological conditions. However, MMP-12 involvement in pulmonary fibrosis is unknown. Here we investigated fibrotic response to bleomycin in MMP-12 deficient mice.
Materials And Methods:
C57BL/6 mice, Balb/c mice and MMP-12 -/- mice with a C57BL/6 background received 0.3 mg bleomycin by intranasal administration. 14 days after, mice were anesthetized and underwent either bronchoalveolear lavage (BAL) or lung removal. Collagen deposition in lung tissue was determined by Sircoltrade mark collagen assay, MMP activity in BAL fluid was analyzed by zymography, and other mediators were quantified in BAL fluid by ELISA. Real time PCR was performed to assess gene expression in lung removed one or 14 days after bleomycin administration. Student t test or Mann & Whitney tests were used when appropriate for statistical analysis.
Results:
The development of pulmonary fibrosis in "fibrosis prone" (C57BL/6) mice was associated with prominent MMP-12 expression in lung, whereas MMP-12 expression was weak in lung tissue of "fibrosis resistant" (Balb/c) mice. MMP-12 mRNA was not detected in MMP-12 -/- mice, in conformity with their genotype. Bleomycin elicited macrophage accumulation in BAL of MMP-12 -/- and wild type (WT) mice, and MMP-12 deficiency had no significant effect on BAL cells composition. Collagen content of lung was increased similarly in MMP-12 -/- and WT mice 14 days after bleomycin administration. Bleomycin elicit a raise of TGF-beta protein, MMP-2 and TIMP-1 protein and mRNA in BAL fluids and lung respectively, and no significant difference was observed between MMP-12 -/- and WT mice considering those parameters.
Conclusion:
The present study shows that MMP-12 deficiency has no significant effect on bleomycin-induced fibrosis.
Insights
Mice lacking macrophage metalloelastase (MMP-12) showed no difference in lung fibrosis development after bleomycin exposure. This suggests MMP-12 is not a key factor in this model of pulmonary fibrosis.
Area of Science:
- Pulmonary Medicine
- Molecular Biology
- Biochemistry
Background:
- Pulmonary fibrosis involves excessive extracellular matrix deposition, leading to respiratory failure.
- Metalloproteinases (MMPs) and their inhibitors (TIMPs) are implicated in fibrosis, but their precise roles are unclear.
- Macrophage metalloelastase (MMP-12) is involved in pathological remodeling, yet its role in pulmonary fibrosis remains unknown.
Purpose of the Study:
- To investigate the role of MMP-12 in bleomycin-induced pulmonary fibrosis.
- To compare fibrotic responses in wild-type and MMP-12 deficient mice.
Main Methods:
- Bleomycin was administered intranasally to C57BL/6, Balb/c, and MMP-12 deficient mice.
- Lung fibrosis was assessed by collagen content, MMP activity, and gene/protein expression of mediators.
- Bronchoalveolar lavage (BAL) and lung tissue analysis were performed 14 days post-administration.
Main Results:
- Pulmonary fibrosis developed similarly in MMP-12 deficient and wild-type mice after bleomycin exposure.
- MMP-12 expression was high in fibrosis-prone mice and low in fibrosis-resistant mice.
- MMP-12 deficiency did not alter macrophage accumulation, collagen deposition, or levels of TGF-beta, MMP-2, and TIMP-1.
Conclusions:
- MMP-12 deficiency does not significantly impact bleomycin-induced pulmonary fibrosis.
- The study indicates MMP-12 is not a critical mediator in this specific model of lung fibrosis.
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