Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-gamma and PTEN.
Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-gamma and PTEN.
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发表时间：
2006
期刊：
影响因子：
64.8
通讯作者：
Min Zhao;Bing Song;Jin Pu;T. Wada;B. Reid;G. Tai;Fei Wang;Aihua Guo;P. Walczysko;Yu Gu
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文献类型：
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作者：
Min Zhao;Bing Song;Jin Pu;T. Wada;B. Reid;G. Tai;Fei Wang;Aihua Guo;P. Walczysko;Yu Gu
伤口愈合对于维持多细胞生物体的完整性至关重要。在研究的每一个物种中，上皮层的破坏会瞬间产生内源性电场，这在伤口愈合中很重要。引导细胞迁移到电线索和电场诱导的伤口愈合的信号通路的身份尚未在遗传水平上阐明。在这里，我们表明，电场的强度等于那些检测内源性，直接细胞迁移在伤口愈合过程中作为一个主要的方向线索。内源性伤口电场的操纵影响体内伤口愈合。电刺激触发Src和肌醇磷脂信号传导的激活，其在细胞迁移的方向上极化。值得注意的是，磷脂酰肌醇-3-OH激酶-γ（PI（3）Kgamma）的遗传破坏降低了电场诱导的信号传导，并消除了愈合上皮响应电信号的定向运动。肿瘤抑制磷酸酶和张力蛋白同源物（PTEN）的缺失增强信号传导和趋电反应。这些数据确定了电信号诱导伤口愈合所必需的基因，并表明PI（3）Kgamma和PTEN控制趋电性。
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-gamma (PI(3)Kgamma) 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)Kgamma and PTEN control electrotaxis.