The actin regulator zyxin reinforces airway smooth muscle and accumulates in airways of fatal asthmatics

Sonia R. Rosner, Christopher D. Pascoe, Elizabeth Blankman, Christopher C. Jensen, Ramaswamy Krishnan, Alan L. James, John G. Elliot, Francis H. Green, Jeffrey C. Liu, Chun Y. Seow, Jin-Ah Park, Mary C. Beckerle, Peter D. Pare, Jeffrey J. Fredberg, Mark A. Smith

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    Abstract

    Bronchospasm induced in non-asthmatic human subjects can be easily reversed by a deep inspiration (DI) whereas bronchospasm that occurs spontaneously in asthmatic subjects cannot. This physiological effect of a DI has been attributed to the manner in which a DI causes airway smooth muscle (ASM) cells to stretch, but underlying molecular mechanisms-and their failure in asthma-remain obscure. Using cells and tissues from wild type and zyxin(-/-) mice we report responses to a transient stretch of physiologic magnitude and duration. At the level of the cytoskeleton, zyxin facilitated repair at sites of stress fiber fragmentation. At the level of the isolated ASM cell, zyxin facilitated recovery of contractile force. Finally, at the level of the small airway embedded with a precision cut lung slice, zyxin slowed airway dilation. Thus, at each level zyxin stabilized ASM structure and contractile properties at current muscle length. Furthermore, when we examined tissue samples from humans who died as the result of an asthma attack, we found increased accumulation of zyxin compared with non-asthmatics and asthmatics who died of other causes. Together, these data suggest a biophysical role for zyxin in fatal asthma.

    Original languageEnglish
    Article number0171728
    Number of pages16
    JournalPLoS One
    Volume12
    Issue number3
    DOIs
    Publication statusPublished - 9 Mar 2017

    Cite this

    Rosner, S. R., Pascoe, C. D., Blankman, E., Jensen, C. C., Krishnan, R., James, A. L., Elliot, J. G., Green, F. H., Liu, J. C., Seow, C. Y., Park, J-A., Beckerle, M. C., Pare, P. D., Fredberg, J. J., & Smith, M. A. (2017). The actin regulator zyxin reinforces airway smooth muscle and accumulates in airways of fatal asthmatics. PLoS One, 12(3), [0171728]. https://doi.org/10.1371/journal.pone.0171728