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.

Fibulin-1 Predicts Disease Progression in Patients With Idiopathic Pulmonary Fibrosis

“…6,7 Th ese include the MUC5B gene polymorphism, 27 mucin-1 (KL-6), surfactant proteins SP-A and SP-D, matrix metalloproteinases 1 and 7, chemokines CCL18 and CXCL8, calgranulin B (S100A12), intracellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion protein 1 (VCAM-1), and periostin. 28 While it is likely that numerous factors will contribute to the development of fi brosis, the strength of our focus on fi bulin-1 is the consistent fi nding in multiple patient cohorts and the multiple forms, soluble and tissue incorporated, of the protein that were increased. In addition, lung tissue fibulin-1 levels relate to physiologic measurements of lung function in patients with IPF.…”

NFκB-Induced Periostin Activates Integrin-β3 Signaling to Promote Renal Injury in GN

“…26 Accordingly, periostin null dermal fibroblasts showed reduced expression of Acta2 and Col1a1 transcripts upon TGF-b1 treatment, 27 whereas mesenchymal cells treated with exogenous periostin showed increased collagen production and wound closure. 28 In a model of acute myocardial infarction, periostin null mice exhibited impaired cardiac healing as a result of reduced myocardial stiffness and collagen fibril formation, whereas inducible overexpression of periostin protected mice from cardiac rupture. 29,30 The ability of periostin to interact and stabilize fibrillar collagens and other extracellular matrix molecules is probably a key event by which periostin controls extracellular matrix deposition and development of fibrosis.…”

“…28,36 We used an alternative strategy of in vivo antisense administration after establishment of severe proteinuria and found that inhibition of periostin could remarkably diminish the inflammation and reverse the increase in proteinuria. The ability of periostin to play distinctive roles in crucial events during development of renal disease by promoting tissue inflammatory response, accumulation of extracellular matrix and podocyte damage underline periostin targeting as a potential efficient future treatment against CKD.…”

Serum lysyl oxidase-like 2 levels and idiopathic pulmonary fibrosis disease progression

“…Future studies should also consider whether sLOXL2, along with other promising prognostic IPF biomarkers (e.g. matrix metalloproteinase (MMP)1, MMP7, KL-6, periostin, surfactant protein-A and D, CC chemokine ligand 18, vascular endothelial growth factor and YKL-40) [19][20][21][22][23][24][25][26][27][28][29], as well as prognostic scores [30,31] and radiological modalities [32], might have prognostic value for helping physicians and patients anticipate the patient's IPF disease progression. This might include evaluation of serially collected sLOXL2 levels and their relationship to IPF acute exacerbations, which represent a terminal event for many IPF patients [33].…”