Epithelial cells in many tissues are regularly subjected to mechanical forces. For example, the alveolar epithelial cells (AECs), which line the lung's inner surface, are exposed to cyclical deformation forces during breathing. During artificial ventilation, these forces dramatically increase and may be deleterious to lung function. On , Jonathan Jones and colleagues test the hypothesis that, in AECs, matrix molecules transduce mechanical signals by interacting with cell-surface receptors. They show that rat AECs secrete a fibrous network of laminin 6 complexed with perlecan, which expands isotropically when exposed to cyclical stretching in vitro. This deformation activates a mitogen-activated protein kinase (MAPK). Function-inhibiting antibodies directed against the α3 subunit of laminin 6 or dystroglycan, a structural protein involved in basement-membrane assembly in epithelial cells, inhibit MAPK activation – as does knocking down dystroglycan by RNAi. Unexpectedly, inhibition of integrins, cell-surface receptors for laminins, does not. The results therefore indicate that participation of laminin 6 in mechanical-signal transduction depends on dystroglycan instead of integrins and suggest that MAPK activation ameliorates any damage caused by AEC overextension during assisted breathing.
