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PNAS 98 (11): 6180-6185

Copyright © 2001 by the National Academy of Sciences.


BIOLOGICAL SCIENCES / CELL BIOLOGY

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

M. A. Swartz*,{dagger}, D. J. Tschumperlin{ddagger}, R. D. Kamm§, and J. M. Drazen*

*Department of Medicine, Pulmonary Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; {ddagger}Physiology Program, Harvard School of Public Health, Boston, MA 02115; and §Department of Mechanical Engineering and Division of Bioengineering and Environmental Health, Massachusetts Institute of Technology, Cambridge, MA 02139

Accepted for publication March 16, 2001.

Received for publication July 18, 2000.

Abstract: Tissue remodeling often reflects alterations in local mechanical conditions and manifests as an integrated response among the different cell types that share, and thus cooperatively manage, an extracellular matrix. Here we examine how two different cell types, one that undergoes the stress and the other that primarily remodels the matrix, might communicate a mechanical stress by using airway cells as a representative in vitro system. Normal stress is imposed on bronchial epithelial cells in the presence of unstimulated lung fibroblasts. We show that (i) mechanical stress can be communicated from stressed to unstressed cells to elicit a remodeling response, and (ii) the integrated response of two cell types to mechanical stress mimics key features of airway remodeling seen in asthma: namely, an increase in production of fibronectin, collagen types III and V, and matrix metalloproteinase type 9 (MMP-9) (relative to tissue inhibitor of metalloproteinase-1, TIMP-1). These observations provide a paradigm to use in understanding the management of mechanical forces on the tissue level.

Key Words: airway wall remodeling • airway epithelium • asthma • lung fibroblasts


{dagger} Present address: Departments of Biomedical and Chemical Engineering, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208.

To whom reprint requests should be addressed. E-mail: jdrazen{at}rics.bwh.harvard.edu.

Communicated by Yuan-Cheng B. Fung, University of California at San Diego, La Jolla, CA

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