Roles of epithelial cell-derived periostin in TGF-beta activation, collagen production, and collagen gel elasticity in asthma.
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-beta signaling pathway in a mechanism involving matrix metalloproteinases 2 and 9. Furthermore, conditioned medium from the epithelial cells overexpressing periostin caused TGF-beta-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-beta activation and collagen gel elasticity in asthma.
Sidhu
Sukhvinder S
SS
Cardiovascular Research Institute, University of California, San Francisco, CA 94143, USA.
Yuan
Shaopeng
S
Innes
Anh L
AL
Kerr
Sheena
S
Woodruff
Prescott G
PG
Hou
Lydia
L
Muller
Susan J
SJ
Fahy
John V
JV
D001249:Asthma / Q000378:metabolism* / Q000473:pathology; D001980:Bronchi / Q000166:cytology / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D004548:Elasticity; D004847:Epithelial Cells / Q000378:metabolism*; D005782:Gels; D006801:Humans; D020782:Matrix Metalloproteinases; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D024042:Collagen Type I; D005782:Gels; C512835:POSTN protein, human; D016212:Transforming Growth Factor beta; D020782:Matrix Metalloproteinases