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 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.
Swartz
M A
MA
Department of Medicine, Pulmonary Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Tschumperlin
D J
DJ
Kamm
R D
RD
Drazen
J M
JM
D001980:Bronchi / Q000166:cytology; D002450:Cell Communication / Q000502:physiology*; D002455:Cell Division; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods; D003094:Collagen / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D051766:Early Growth Response Protein 1; D004847:Epithelial Cells / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000096:biosynthesis; D006801:Humans; D017874:Immediate-Early Proteins; D008168:Lung / Q000166:cytology; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D020545:Respiratory Mucosa / Q000166:cytology; D015398:Signal Transduction / Q000502:physiology*; D013314:Stress, Mechanical; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis
D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D005353:Fibronectins; D017874:Immediate-Early Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D014157:Transcription Factors; D003094:Collagen; D020780:Matrix Metalloproteinase 9