Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-γ 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 V. Forrester; Henry R. Bourne; Peter N. Devreotes; Colin D. McCaig; Josef M. Penninger

doi:10.1038/nature04925

Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-γ 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 V. Forrester, Henry R. Bourne, Peter N. Devreotes, Colin D. McCaig, Josef M. Penninger

School of Medicine

Research output: Contribution to journal › Article › peer-review

596 Scopus citations

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. 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-γ (PI(3)Kγ) 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)Kγ and PTEN control electrotaxis.

Original language	English (US)
Pages (from-to)	457-460
Number of pages	4
Journal	Nature
Volume	442
Issue number	7101
DOIs	https://doi.org/10.1038/nature04925
State	Published - Jul 27 2006

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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-γ and PTEN. Nature, 442(7101), 457-460. https://doi.org/10.1038/nature04925

@article{4ff3e3c3676c4a6b9391fbeda87dbcb5,

title = "Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-γ and PTEN",

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. 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-γ (PI(3)Kγ) 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)Kγ and PTEN control electrotaxis.",

author = "Min Zhao and Bing Song and Jin Pu and Teiji Wada and Brian Reid and Guangping Tai and Fei Wang and Aihua Guo and Petr Walczysko and Yu Gu and Takehiko Sasaki and Akira Suzuki and Forrester, {John V.} and Bourne, {Henry R.} and Devreotes, {Peter N.} and McCaig, {Colin D.} and Penninger, {Josef M.}",

note = "Funding Information: Acknowledgements This work was supported by grants from the Wellcome Trust and Royal Society (to M.Z.), the Institute of Molecular Biotechnology of Austria of the Austrian Academy of Sciences, the Austria Ministry of Sciences, the Austrian National Bank, and a European Union Framework 6 excellence grant (all to J.M.P.). We thank all members of the Zhao, Bourne and Penninger laboratories for discussions and technical assistance. Copyright: Copyright 2015 Elsevier B.V., All rights reserved.",

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doi = "10.1038/nature04925",

language = "English (US)",

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AU - Zhao, Min

AU - Song, Bing

AU - Pu, Jin

AU - Wada, Teiji

AU - Reid, Brian

AU - Tai, Guangping

AU - Wang, Fei

AU - Guo, Aihua

AU - Walczysko, Petr

AU - Gu, Yu

AU - Sasaki, Takehiko

AU - Suzuki, Akira

AU - Forrester, John V.

AU - Bourne, Henry R.

AU - Devreotes, Peter N.

AU - McCaig, Colin D.

AU - Penninger, Josef M.

N1 - Funding Information: Acknowledgements This work was supported by grants from the Wellcome Trust and Royal Society (to M.Z.), the Institute of Molecular Biotechnology of Austria of the Austrian Academy of Sciences, the Austria Ministry of Sciences, the Austrian National Bank, and a European Union Framework 6 excellence grant (all to J.M.P.). We thank all members of the Zhao, Bourne and Penninger laboratories for discussions and technical assistance. Copyright: Copyright 2015 Elsevier B.V., All rights reserved.

PY - 2006/7/27

Y1 - 2006/7/27

N2 - 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. 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-γ (PI(3)Kγ) 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)Kγ and PTEN control electrotaxis.

AB - 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. 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-γ (PI(3)Kγ) 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)Kγ and PTEN control electrotaxis.

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

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