Expression of 150-kDa oxygen-regulated protein (ORP150) stimulates bleomycin-induced pulmonary fibrosis and dysfunction in mice

Ken Ichiro Tanaka, Ayano Shirai, Yosuke Ito, Takushi Namba, Kayoko Tahara, Naoki Yamakawa, Tohru Mizushima

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)818-824
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume425
Issue number4
DOIs
Publication statusPublished - 2012 Sep 7

Fingerprint

Pulmonary Fibrosis
Bleomycin
Transforming Growth Factors
Myofibroblasts
Lung
Idiopathic Pulmonary Fibrosis
Lung Injury
Respiratory Mechanics
Endoplasmic Reticulum Stress
oxygen-regulated proteins
Mechanics
Endoplasmic Reticulum
Fibrosis
Maintenance
Proteins

Keywords

  • Bleomycin
  • IPF
  • Myofibroblast
  • ORP150
  • TGF-β1

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Expression of 150-kDa oxygen-regulated protein (ORP150) stimulates bleomycin-induced pulmonary fibrosis and dysfunction in mice. / Tanaka, Ken Ichiro; Shirai, Ayano; Ito, Yosuke; Namba, Takushi; Tahara, Kayoko; Yamakawa, Naoki; Mizushima, Tohru.

In: Biochemical and Biophysical Research Communications, Vol. 425, No. 4, 07.09.2012, p. 818-824.

Research output: Contribution to journalArticle

Tanaka, Ken Ichiro ; Shirai, Ayano ; Ito, Yosuke ; Namba, Takushi ; Tahara, Kayoko ; Yamakawa, Naoki ; Mizushima, Tohru. / Expression of 150-kDa oxygen-regulated protein (ORP150) stimulates bleomycin-induced pulmonary fibrosis and dysfunction in mice. In: Biochemical and Biophysical Research Communications. 2012 ; Vol. 425, No. 4. pp. 818-824.
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