Role of heat shock protein 27 in cytoskeletal remodeling of the airway smooth muscle cell

Steven S. An, Ben Fabry, Mathew Mellema, Predrag Bursac, William T. Gerthoffer, Usamah S. Kayyali, Matthias Gaestel, Stephanie A. Shore, Jeffrey J. Fredberg

Research output: Contribution to journalArticle

Abstract

Remodeling of the airway smooth muscle (ASM) cell has been proposed to play an important role in airway hyperresponsiveness. Using a functional assay, we have assessed remodeling of the cultured rat ASM cell and the role of heat shock protein (HSP) 27 in that process. To probe remodeling dynamics, we measured spontaneous motions of an individual Arg-Gly-Aspcoated microbead that was anchored to the cytoskeleton. We reasoned that the bead could not move unless the microstructure to which it is attached rearranged; if so, then its mean square displacement (MSD) would report ongoing internal reorganizations over time. Each bead displayed a random, superdiffusive motion; MSD increased with time as ∼t1.7, whereas an exponent of unity would be expected for a simple passive diffusion. Increasing concentrations of cytochalasin-D or latrunculin-A caused marked increases in the MSD, whereas colchicine did not. Treatments with PDGF or IL-1β, but not transforming growth factor-β, caused decreases in the MSD, the extent of which rank-ordered with the relative potency of these agents in eliciting the phosphorylation of HSP27. The chemical stressors anisomycin and arsenite each increased the levels of HSP27 phosphorylation and, at the same time, decreased bead motions. In particular, arsenite prevented and even reversed the effects of cytochalasin-D on bead motions. Finally, ASM cells overexpressing phospho-mimicking human HSP27, but not wild-type or phosphorylation-deficient HSP27, exhibited decreases in bead motions that were comparable to the arsenite response. Taken together, these results show that phosphorylated HSP27 favors reduced bead motions that are probably due to stabilization of the actin cytoskeleton.

Original languageEnglish (US)
Pages (from-to)1701-1713
Number of pages13
JournalJournal of applied physiology
Volume96
Issue number5
DOIs
StatePublished - May 1 2004
Externally publishedYes

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Keywords

  • Actin dynamics
  • Cytoskeleton
  • Diffusion
  • Plasticity
  • Superdiffusion

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

An, S. S., Fabry, B., Mellema, M., Bursac, P., Gerthoffer, W. T., Kayyali, U. S., Gaestel, M., Shore, S. A., & Fredberg, J. J. (2004). Role of heat shock protein 27 in cytoskeletal remodeling of the airway smooth muscle cell. Journal of applied physiology, 96(5), 1701-1713. https://doi.org/10.1152/japplphysiol.01129.2003