A role for p38(MAPK)/HSP27 pathway in smooth muscle cell migration

Jason C. Hedges, Melissa A. Dechert, Ilia A. Yamboliev, Jody L. Martin, Eileen Hickey, Lee A. Weber, William T. Gerthoffer

Research output: Contribution to journalArticle

338 Scopus citations

Abstract

Smooth muscle cells are exposed to growth factors and cytokines that contribute to pathological states including airway hyperresponsiveness, atherosclerosis, angiogenesis, smooth muscle hypertrophy, and hyperplasia. A common feature of several of these conditions is migration of smooth muscle beyond the initial boundary of the organ. Signal transduction pathways activated by extracellular signals that instigate migration are mostly undefined in smooth muscles. We measured migration of cultured tracheal myocytes in response to platelet-derived growth factor, interleukin-1β, and transforming growth factor-β. Cellular migration was blocked by SB203580, an inhibitor of p38(MAPK). Time course experiments demonstrated increased phosphorylation of p38(MAPK). Activation of p38(MAPK) resulted in the phosphorylation of HSP27 (heat shock protein 277), which may modulate F-actin polymerization. Inhibition of p38(MAPK) activity inhibited phosphorylation of HSP27. Adenovirus-mediated expression of activated mutant MAPK kinase 6b(E), an upstream activator for p38(MAPK), increased cell migration, whereas overexpression of p38α MAPK dominant negative mutant and an HSP27 phosphorylation mutant blocked cell migration completely. The results indicate that activation of the p38(MAPK) pathway by growth factors and proinflammatory cytokines regulates smooth muscle cell migration and may contribute to pathological states involving smooth muscle dysfunction.

Original languageEnglish (US)
Pages (from-to)24211-24219
Number of pages9
JournalJournal of Biological Chemistry
Volume274
Issue number34
DOIs
StatePublished - Aug 20 1999

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Hedges, J. C., Dechert, M. A., Yamboliev, I. A., Martin, J. L., Hickey, E., Weber, L. A., & Gerthoffer, W. T. (1999). A role for p38(MAPK)/HSP27 pathway in smooth muscle cell migration. Journal of Biological Chemistry, 274(34), 24211-24219. https://doi.org/10.1074/jbc.274.34.24211