Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-gamma and PTEN

Min Zhao, Bing Song, Jin Pu, Teiji Wada, Brian Reid, Guangping Tai, Fei Wang, Aihua Guo, Petr Walczysko, Yu Gu, Takehiko Sasaki, Akira Suzuki, John Vincent Forrester, Henry R. Bourne, Peter N. Devreotes, Colin Darnley McCaig, Josef M. Penninger

Research output: Contribution to journalArticle

566 Citations (Scopus)

Abstract

Wound healing is essential for maintaining the integrity of multicellular organisms. In every species studied, disruption of an epithelial layer instantaneously generates endogenous electric fields, which have been proposed to be important in wound healing(1-3). The identity of signalling pathways that guide both cell migration to electric cues and electric-field-induced wound healing have not been elucidated at a genetic level. Here we show that electric fields, of a strength equal to those detected endogenously, direct cell migration during wound healing as a prime directional cue. Manipulation of endogenous wound electric fields affects wound healing in vivo. Electric stimulation triggers activation of Src and inositol - phospholipid signalling, which polarizes in the direction of cell migration. Notably, genetic disruption of phosphatidylinositol-3-OH kinase-gamma (PI( 3) K gamma) decreases electric-field-induced signalling and abolishes directed movements of healing epithelium in response to electric signals. Deletion of the tumour suppressor phosphatase and tensin homolog (PTEN) enhances signalling and electrotactic responses. These data identify genes essential for electrical-signal-induced wound healing and show that PI(3) K gamma and PTEN control electrotaxis.

Original languageEnglish
Pages (from-to)457-460
Number of pages4
JournalNature
Volume442
DOIs
Publication statusPublished - 27 Jul 2006

Keywords

  • chemicoattractant gradients
  • in vivo
  • chemotaxis
  • fields
  • orientation
  • migration
  • currents
  • cells
  • polarization
  • regeneration

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    Zhao, M., Song, B., Pu, J., Wada, T., Reid, B., Tai, G., Wang, F., Guo, A., Walczysko, P., Gu, Y., Sasaki, T., Suzuki, A., Forrester, J. V., Bourne, H. R., Devreotes, P. N., McCaig, C. D., & Penninger, J. M. (2006). Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-gamma and PTEN. Nature, 442, 457-460. https://doi.org/10.1038/nature04925