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.
|Number of pages||7|
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - 2012 Sep 7|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology