Periostin promotes fibrosis and predicts progression in patients with idiopathic pulmonary fibrosis

Payal K. Naik, Paul D. Bozyk, J. Kelley Bentley, Antonia P. Popova, Carolyn M. Birch, Carol A. Wilke, Christopher D. Fry, Eric S. White, Thomas H. Sisson, Nabihah Tayob, Barbara Carnemolla, Paola Orecchia, Kevin R. Flaherty, Marc B. Hershenson, Susan Murray, Fernando J. Martinez, Bethany B. Moore

Research output: Contribution to journalArticle

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Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease without effective therapeutics. Periostin has been reported to be elevated in IPF patients relative to controls, but its sources and mechanisms of action remain unclear. We confirm excess periostin in lungs of IPF patients and show that IPF fibroblasts produce periostin. Blood was obtained from 54 IPF patients (all but 1 with 48 wk of follow-up). We show that periostin levels predict clinical progression at 48 wk (hazard ratio = 1.47, 95% confidence interval = 1.03-2.10, P <0.05). Monocytes and fibrocytes are sources of periostin in circulation in IPF patients. Previous studies suggest that periostin may regulate the inflammatory phase of bleomycin-induced lung injury, but periostin effects during the fibroproliferative phase of the disease are unknown. Wild-type and periostin-deficient (periostin-/-) mice were anesthetized and challenged with bleomycin. Wild-type mice were injected with bleomycin and then treated with OC-20 Ab (which blocks periostin and integrin interactions) or control Ab during the fibroproliferative phase of disease, and fibrosis and survival were assessed. Periostin expression was upregulated quickly after treatment with bleomycin and remained elevated. Periostin-/- mice were protected from bleomycin-induced fibrosis. Instillation of OC-20 during the fibroproliferative phase improved survival and limited collagen deposition. Chimeric mouse studies suggest that hematopoietic and structural sources of periostin contribute to lung fibrogenesis. Periostin was upregulated by transforming growth factor-β in lung mesenchymal cells, and periostin promoted extracellular matrix deposition, mesenchymal cell proliferation, and wound closure. Thus periostin plays a vital role in late stages of pulmonary fibrosis and is a potential biomarker for disease progression and a target for therapeutic intervention.

Original languageEnglish
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume303
Issue number12
DOIs
Publication statusPublished - Dec 15 2012

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Idiopathic Pulmonary Fibrosis
Bleomycin
Fibrosis
Lung
Survival
Pulmonary Fibrosis
Lung Injury
Transforming Growth Factors
Integrins
Lung Diseases
Extracellular Matrix
Disease Progression
Monocytes
Collagen
Therapeutics
Fibroblasts
Biomarkers
Cell Proliferation
Confidence Intervals
Wounds and Injuries

Keywords

  • Bleomycin
  • Fibroblast
  • Lung
  • Mesenchymal

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology
  • Physiology

Cite this

Periostin promotes fibrosis and predicts progression in patients with idiopathic pulmonary fibrosis. / Naik, Payal K.; Bozyk, Paul D.; Kelley Bentley, J.; Popova, Antonia P.; Birch, Carolyn M.; Wilke, Carol A.; Fry, Christopher D.; White, Eric S.; Sisson, Thomas H.; Tayob, Nabihah; Carnemolla, Barbara; Orecchia, Paola; Flaherty, Kevin R.; Hershenson, Marc B.; Murray, Susan; Martinez, Fernando J.; Moore, Bethany B.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 303, No. 12, 15.12.2012.

Research output: Contribution to journalArticle

Naik, PK, Bozyk, PD, Kelley Bentley, J, Popova, AP, Birch, CM, Wilke, CA, Fry, CD, White, ES, Sisson, TH, Tayob, N, Carnemolla, B, Orecchia, P, Flaherty, KR, Hershenson, MB, Murray, S, Martinez, FJ & Moore, BB 2012, 'Periostin promotes fibrosis and predicts progression in patients with idiopathic pulmonary fibrosis', American Journal of Physiology - Lung Cellular and Molecular Physiology, vol. 303, no. 12. https://doi.org/10.1152/ajplung.00139.2012
Naik, Payal K. ; Bozyk, Paul D. ; Kelley Bentley, J. ; Popova, Antonia P. ; Birch, Carolyn M. ; Wilke, Carol A. ; Fry, Christopher D. ; White, Eric S. ; Sisson, Thomas H. ; Tayob, Nabihah ; Carnemolla, Barbara ; Orecchia, Paola ; Flaherty, Kevin R. ; Hershenson, Marc B. ; Murray, Susan ; Martinez, Fernando J. ; Moore, Bethany B. / Periostin promotes fibrosis and predicts progression in patients with idiopathic pulmonary fibrosis. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2012 ; Vol. 303, No. 12.
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