Journal
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
Volume 20, Issue 6, Pages 674-682Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcdb.2008.12.009
Keywords
Wound healing; Electric fields; Cell migration; Guidance cue; Hierarchical signaling; Overriding guidance; Transepithelial potential difference
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Funding
- Wellcome Trust
- Mearns' Trust
- British Heart Foundation
- Royal Society (London)
- Royal Society of Edinburgh
- UC Davis Dermatology
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Injury that disrupts an epithelial layer instantaneously generates endogenous electric fields (EFs), which were detected at human skin wounds over 150 years ago. Recent researches combining molecular, genetic and imaging techniques have provided significant insights into cellular and molecular responses to this unconventional signal. One unexpected finding is that the EFs play an overriding guidance role in directing cell migration in epithelialwound healing. In experimental models where other directional cues (e. g., contact inhibition release, population pressure etc.) are present, electric fields of physiological strength override them and direct cell migration. The electrotaxis or galvanotaxis is mediated by polarized activation of multiple signaling pathways that include PI3 kinases/Pten, membrane growth factor receptors and integrins. Genetic manipulation of PI3 kinase/Pten (Phosphoinositide 3-kinases/phosphatase and tensin homolog) and integrin beta 4 demonstrated the importance of those molecules. The electric fields are therefore a fundamental signal that directs cell migration in wound healing. One of the most challenging question is: How do cells sense the very weak electric signals? Clinically, it is highly desirable to develop practical and reliable technologies for wound healing management exploiting the electric signaling. (C) 2008 Elsevier Ltd. All rights reserved.
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