Roles of Periostin in Respiratory Disorders

Abstract

Periostin is a matricellular protein that has been implicated in many disease states. It interacts with multiple signaling cascades to modulate the expression of downstream genes that regulate cellular interactions within the extracellular matrix. This review focuses on the role of periostin in respiratory diseases, including asthma and idiopathic pulmonary fibrosis, and its potential to help guide treatment or assess prognosis. Epithelial injury is a common feature of many respiratory diseases, resulting in the secretion, among others, of periostin, which is subsequently involved in airway remodeling and other aspects of pulmonary pathophysiology. In asthma, periostin is recognized as a biomarker of type 2 inflammation; POSTN gene expression is up-regulated in bronchial epithelial cells by IL-13 and IL-4. Serum periostin has been evaluated for the identification of patients with increased clinical benefit from treatment with anti-IL-13 (lebrikizumab, tralokinumab) and anti-IgE (omalizumab) therapy and may be prognostic for increased risk of asthma exacerbations and progressive lung function decline. Furthermore, in asthma, periostin may regulate subepithelial fibrosis and mucus production and may serve as a systemic biomarker of eosinophilic airway inflammation. Periostin is also highly expressed in the lungs of patients with idiopathic pulmonary fibrosis, and its serum levels may predict clinical progression. Overall, periostin contributes to multiple pathogenic processes across respiratory diseases, and peripheral blood levels of periostin may have utility as a biomarker of treatment response and disease progression.

Keywords: airway remodeling; asthma; biomarker; idiopathic pulmonary fibrosis; periostin.

Figure 1.

Secretion of periostin in the airway in response to IL-13 and proposed actions in asthma and idiopathic pulmonary fibrosis (IPF). Th2 = T-helper cell type 2.

Figure 2.

Pleiotropic effects of periostin. Inflammatory cells (lymphocytes, neutrophils, and macrophages) release cytokines to induce periostin secretion from stromal cells. Periostin binds to eosinophils, mediating eosinophil localization, adhesion, and recruitment to airways. After an inflammatory stimulus, periostin derived from epithelial airway cells activates transforming growth factor (TGF)-β and up-regulates type I collagen. Periostin acts on fibroblasts, activating nuclear factor-κB and promoting the expression of inflammatory cytokines and chemokines. Periostin induces differentiation of fibroblasts to myofibroblasts. By binding to other extracellular matrix (ECM) proteins and inducing collagen fibrillogenesis and cross-linking, periostin enhances fibrosis.