Roles of epithelial cell-derived periostin in TGF-β activation, collagen production, and collagen gel elasticity in asthma

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 107; no. 32; pp. 14170 - 14175
• Main Authors: Sidhu, Sukhvinder S., Yuan, Shaopeng, Innes, Anh L., Kerr, Sheena, Woodruff, Prescott G., Hou, Lydia, Muller, Susan J., Fahy, John V., Yamamoto, Keith R.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 10.08.2010; National Acad Sciences
• Subjects: Asthma; Asthma - metabolism; Asthma - pathology; Biological Sciences; Bronchi - cytology; Bronchi - pathology; Business to business; Cell Adhesion Molecules - physiology; Cells, Cultured; collagen; Collagen Type I - biosynthesis; Collagen Type I - chemistry; Collagen Type I - secretion; Collagens; crosslinking; Elasticity; Epithelial cells; Epithelial Cells - metabolism; epithelium; extracellular matrix; Fibroblasts; Fibrosis; Gels; Gene expression; gene expression regulation; Humans; in situ hybridization; interleukin-13; Matrix Metalloproteinases; metalloproteinases; mixing; Moduli of elasticity; modulus of elasticity; protein synthesis; secretion; signal transduction; transforming growth factor beta; Transforming Growth Factor beta - metabolism; Up regulation
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.1009426107

Periostin is considered to be a matricellular protein with expression typically confined to cells of mesenchymal origin. Here, by using in situ hybridization, we show that periostin is specifically up-regulated in bronchial epithelial cells of asthmatic subjects, and in vitro, we show that periostin protein is basally secreted by airway epithelial cells in response to IL-13 to influence epithelial cell function, epithelial–mesenchymal interactions, and extracellular matrix organization. In primary human bronchial epithelial cells stimulated with periostin and epithelial cells overexpressing periostin, we reveal a function for periostin in stimulating the TGF-β signaling pathway in a mechanism involving matrix metalloproteinases 2 and 9. Furthermore, conditioned medium from the epithelial cells overexpressing periostin caused TGF-β–dependent secretion of type 1 collagen by airway fibroblasts. In addition, mixing recombinant periostin with type 1 collagen in solution caused a dramatic increase in the elastic modulus of the collagen gel, indicating that periostin alters collagen fibrillogenesis or cross-linking and leads to stiffening of the matrix. Epithelial cell-derived periostin in asthma has roles in TGF-β activation and collagen gel elasticity in asthma.