title: Periostin promotes fibrosis and predicts progression in patients with idiopathic pulmonary fibrosis.
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.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Payal K
authors.initials: PK
authors.lastname: Naik
authors.forename: Paul D
authors.initials: PD
authors.lastname: Bozyk
authors.forename: J Kelley
authors.initials: JK
authors.lastname: Bentley
authors.forename: Antonia P
authors.initials: AP
authors.lastname: Popova
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Birch
authors.forename: Carol A
authors.initials: CA
authors.lastname: Wilke
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Fry
authors.forename: Eric S
authors.initials: ES
authors.lastname: White
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Sisson
authors.forename: Nabihah
authors.initials: N
authors.lastname: Tayob
authors.forename: Barbara
authors.initials: B
authors.lastname: Carnemolla
authors.forename: Paola
authors.initials: P
authors.lastname: Orecchia
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Flaherty
authors.forename: Marc B
authors.initials: MB
authors.lastname: Hershenson
authors.forename: Susan
authors.initials: S
authors.lastname: Murray
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Martinez
authors.forename: Bethany B
authors.initials: BB
authors.lastname: Moore
mesh_terms: D000368:Aged; D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D015415:Biomarkers; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000097:blood*; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism; D018450:Disease Progression; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000378:metabolism*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014945:Wound Healing
chemical_list: D057134:Antibodies, Neutralizing; D015415:Biomarkers; D015815:Cell Adhesion Molecules; C512835:POSTN protein, human; C082838:Postn protein, mouse; D016212:Transforming Growth Factor beta; D003094:Collagen