Potential mechanosensory mechanisms in airway epithelial cells exposed to a transcellular pressure difference

摘要

Previous research has shown that the pattern of constriction in asthmatic airways increases compressive stresses at the epithelial surface. In vitro, a compressive transcellular pressure difference caused airway epithelial cells to upregulate early growth response-l (EGR-l) and transforming growth factor-β(TGF-β), which have been implicated in airway wall remodeling in asthmatic airways [2]. How the epithelial cells sense a transcellular pressure and convert it into a biological signal is still unknown. A finite-element model of an epithelial cell on a porous substrate was created in order to investigate possible mechanisms for mechanotransduction in the airways. A 2kPa pressure difference applied across the cell caused the basal cell surface to deform in the porous substrate, increasing membrane and cytoskeletal stresses in the vicinity of the pore. In addition, Transmission Electron Microscope (TEM) and Two-Photon Microscopy (TPM) showed the existence of fluid pools between the epithelial cells. In addition to localized deformations, a transcellular pressure may also cause a net transport of fluid from the surface to the lateral intercellular spaces between the epithelial cells. The fluid pools were most pronounced after pressurization in the areas where three or more cells come together. Two-photon images taken while the cell layer was pressurized showed an increase in the width of the lateral intercellular spaces， and decreases in the epithelial layer height and in the amount of fluid bathing the apical surface. It is hypothesized that deformation of the cells into the porous substrate creates a seal, preventing fluid from leaving the intercellular spaces.