Airway Smooth Muscle Resolidification Following Stretch Is Dependent On Zyxin

Abstract

In response to a transient mechanical stretch, the airway smooth muscle (ASM) cell is found to promptly fluidize and then slowly resolidify. While fluidization is typified by prompt reduction of cytoskeletal stiffness and cell contractile forces, and a loss of actin stress fibers, resolidification is typified by a slow restoration of these same material properties. This resolidification response is ATP-dependent, moreover, and hence presumed to be driven by active molecular interactions. A likely candidate for regulation of these molecular interactions is the LIM protein zyxin, which is known to localize to actin stress fibers in response to stretch, and to stabilize actin stress -actinin fibers by recruiting VASP and α . Here we tested the hypothesis that zyxin mediates the resolidification response. Using unpassaged primary ASM cells isolated from the tracheas of WT and zyxin-/-mice, we measured changes in cell contractile force (represented by a scalar metric called the contractile moment) after transient stretch using Fourier transform traction microscopy. Following a transient isotropic stretch (5-10% strain), contractile force in WT ASM cells returned to baseline within 300 seconds, whereas contractile force in essential for zyxin-/-cells returned to only 80% of baseline within 500 seconds, (Figure 1). Based on this evidence, we suggest that zyxin is full recovery of contractile forces in a dynamic microenvironment and thereby provides a potential target for modulating contractile dynamics in ASM. Figure 1. Recovery of Contractile Force Following Transient Isotropic Stretch in WT and Zyxin-/-Primary ASM This abstract is funded by: None Am J Respir Crit Care Med 185;2012:A4130 Internet address: www.atsjournals.org Online Abstracts Issue

Gene expression in asthmatic airway smooth muscle: a mixed bag

“…For example, there has been interesting work looking at the expression of actin binding proteins, like zyxin (Rosner et al 2014), which appears to play a role in stabilizing the cytoskeleton and stiffening ASM cells. Changes in expression of this protein could make asthmatic ASM more resistant to strain and could account for the results seen by Chin et al (2012).…”