Cardiovascular Research Institute, University of California, San Francisco, CA 94143, USA.
Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14170-5. doi: 10.1073/pnas.1009426107. Epub 2010 Jul 26.
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.
骨膜蛋白被认为是一种基质细胞蛋白，其表达通常局限于间充质来源的细胞。在这里，通过原位杂交，我们显示骨膜蛋白在哮喘患者的支气管上皮细胞中特异性地上调，并且在体外，我们显示骨膜蛋白蛋白基底分泌气道上皮细胞对白细胞介素-13 反应，以影响上皮细胞功能，上皮-间充质相互作用和细胞外基质组织。在原代人支气管上皮细胞中用骨膜蛋白刺激和过表达骨膜蛋白的上皮细胞，我们揭示了骨膜蛋白在刺激 TGF-β信号通路中的作用，该机制涉及基质金属蛋白酶 2 和 9。此外，过表达骨膜蛋白的上皮细胞的条件培养基导致气道成纤维细胞依赖 TGF-β分泌 I 型胶原。此外，将重组骨膜蛋白与溶液中的 I 型胶原混合会导致胶原凝胶弹性模量的显著增加，表明骨膜蛋白改变胶原原纤维形成或交联并导致基质变硬。哮喘中上皮细胞衍生的骨膜蛋白在 TGF-β激活和胶原凝胶弹性中起作用。
