Mechanical stress is communicated between different cell types to elicit matrix remodeling

Tissue remodeling often reflects alterations in local mechanical conditions and manifests as an integrated response among the different cell types tha t share, and thus cooperatively manage, an extracellular matrix. Here we ex amine how two different cell types, one that undergoes the stress and the o ther that primarily remodels the matrix, might communicate a mechanical str ess by using airway cells as a representative in vitro system. Normal stres s is imposed on bronchial epithelial cells in the presence of unstimulated lung fibroblasts. We show that (i) mechanical stress can be communicated fr om stressed to unstressed cells to elicit a remodeling response, and (ii) t he integrated response of two cell types to mechanical stress mimics key fe atures of airway remodeling seen in asthma: namely, an increase in producti on of fibronectin, collagen types III and V, and matrix metalloproteinase t ype 9 (MMP-9) (relative to tissue inhibitor of metalloproteinase-1, TIMP-1) , These observations provide a paradigm to use in understanding the managem ent of mechanical forces on the tissue level.