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Updated: May 19, 2026
Oropharyngeal Administration of Bleomycin in the Murine Model of Pulmonary Fibrosis
Published on: May 9, 2025
Expression of 150-kDa oxygen-regulated protein (ORP150) stimulates bleomycin-induced pulmonary fibrosis and
Ken-Ichiro Tanaka1, Ayano Shirai, Yosuke Ito
1Department of Analytical Chemistry, Faculty of Pharmacy, Keio University, Tokyo 105-8512, Japan.
Abstract:
Idiopathic pulmonary fibrosis (IPF) involves pulmonary injury associated with inflammatory responses, fibrosis and dysfunction. Myofibroblasts and transforming growth factor (TGF)-β1 play major roles in the pathogenesis of this disease. Endoplasmic reticulum (ER) stress response is induced in the lungs of IPF patients. One of ER chaperones, the 150-kDa oxygen-regulated protein (ORP150), is essential for the maintenance of cellular viability under stress conditions. In this study, we used heterozygous ORP150-deficient mice (ORP150(+/-) mice) to examine the role of ORP150 in bleomycin-induced pulmonary fibrosis. Treatment of mice with bleomycin induced the expression of ORP150 in the lung. Bleomycin-induced inflammatory responses were slightly exacerbated in ORP150(+/-) mice compared to wild-type mice. On the other hand, bleomycin-induced pulmonary fibrosis, alteration of lung mechanics and respiratory dysfunction was clearly ameliorated in the ORP150(+/-) mice. Bleomycin-induced increases in pulmonary levels of both active TGF-β1 and myofibroblasts were suppressed in ORP150(+/-) mice. These results suggest that although ORP150 is protective against bleomycin-induced lung injury, this protein could stimulate bleomycin-induced pulmonary fibrosis by increasing pulmonary levels of TGF-β1 and myofibroblasts.
Insights
The 150-kDa oxygen-regulated protein (ORP150) may protect against lung injury but appears to worsen pulmonary fibrosis by increasing TGF-β1 and myofibroblasts in idiopathic pulmonary fibrosis models.
Area of Science:
- Pulmonary Medicine
- Cellular Biology
- Fibrosis Research
Background:
- Idiopathic pulmonary fibrosis (IPF) is characterized by lung injury, inflammation, and fibrosis.
- Myofibroblasts and transforming growth factor-β1 (TGF-β1) are key players in IPF pathogenesis.
- Endoplasmic reticulum (ER) stress is observed in IPF lungs, with ORP150 being a crucial ER chaperone for cellular survival.
Purpose of the Study:
- To investigate the role of ORP150 in bleomycin-induced pulmonary fibrosis using heterozygous ORP150-deficient mice.
- To determine if ORP150 influences inflammatory responses, fibrosis development, and lung function in a preclinical model of lung injury.
Main Methods:
- Utilized heterozygous ORP150-deficient mice (ORP150(+/-)) and wild-type littermates.
- Administered bleomycin to induce pulmonary fibrosis and lung injury.
- Assessed inflammatory responses, pulmonary fibrosis, lung mechanics, respiratory function, TGF-β1 levels, and myofibroblast populations.
Main Results:
- Bleomycin induced ORP150 expression in the lungs.
- Inflammatory responses to bleomycin were slightly increased in ORP150(+/-) mice.
- Pulmonary fibrosis, altered lung mechanics, and respiratory dysfunction were significantly reduced in ORP150(+/-) mice.
- Bleomycin-induced increases in active TGF-β1 and myofibroblasts were suppressed in ORP150(+/-) mice.
Conclusions:
- ORP150 appears protective against acute bleomycin-induced lung injury.
- However, ORP150 may promote bleomycin-induced pulmonary fibrosis by upregulating TGF-β1 and myofibroblasts.
- These findings suggest a complex, dual role for ORP150 in the context of lung injury and fibrosis.
