2006
DOI: 10.1038/nature04925
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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, … Show more

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Cited by 882 publications
(961 citation statements)
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References 29 publications
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“…Dunkin et al 1 found that skin cuts to a depth of 0.5-0.6 mm close by electrical cell stimulation without any trace of scar tissue. Zhao et al 2 reported similar effects of electrical currents on cell motility and healing. Deeper skin cuts close by ''skin repair'' that ultimately results in scar formation Figure 1.…”
mentioning
confidence: 83%
“…Dunkin et al 1 found that skin cuts to a depth of 0.5-0.6 mm close by electrical cell stimulation without any trace of scar tissue. Zhao et al 2 reported similar effects of electrical currents on cell motility and healing. Deeper skin cuts close by ''skin repair'' that ultimately results in scar formation Figure 1.…”
mentioning
confidence: 83%
“…PI3K signalling can promote proinflammatory cytokine production by activating nuclear factor‐κB (NFκB) downstream of AKT and can mediate IL‐6 expression, which, in our study, was down‐regulated by microcurrent 33. TGF‐β plays a central role in the induction of fibrosis by stimulation of the Smad system, which in turn increases the expression of collagen types I, III, and VI and accelerates the production of extracellular matrix proteins 31. Microcurrent‐induced down‐regulation of TGF‐β is expected to up‐regulate the expression of PTEN, with the consequence of inhibiting PI3Kγ, which exerts an antifibrotic and contractility‐enhancing effect 34…”
Section: Discussionmentioning
confidence: 59%
“…Thus, it is conceivable that the external application of a microcurrent could normalize the endogenous electrical gradient, either by influencing the existing current gradient or by triggering protein activation to induce favourable cellular responses 30. Initial evidence showing that electrical signals can modulate kinase activity was reported in a paper published by Zhao and colleagues in Nature 31. They found that electrical signals control wound healing in injured skin by phosphoinositide‐3 kinase isoform γ (PI3Kγ), which can be seen as a transformer of electrical cues into biological cues.…”
Section: Discussionmentioning
confidence: 99%
“…The hypothesis that wound repair is guided by electric signals is supported by three main lines of evidence: (1) Strong electric currents exist at wounds and are required for effective wound healing; [9][10][11][12][13] (2) inhibition of endogenous currents specifically impairs wound closure; 13,14 and (3) applying an exogenous electric current of physiological intensity can induce faster wound closure both in vitro and in vivo. [3][4][5][6][7][8]14 In this review, we have compiled the present knowledge on the effects that electric fields (EFs) have on the behavior of cells involved in the healing response, and we focus on the mechanistic understanding of how electric signals are sensed and transmitted within these cells to influence their physiological behavior. In addition, we explore the potential of interfering with EF signaling to enhance skin wound repair by highlighting the potential of dual therapies using pharmacological compounds that regulate phosphorylation signaling and ES of wounds.…”
Section: Scope and Significancementioning
confidence: 99%
“…In vitro and Phase I preclinical studies in animal models of wound healing will be useful to assess the potential of these dual therapies to treat nonhealing wounds. 14 …”
Section: Scope and Significancementioning
confidence: 99%