TY - JOUR
T1 - Electric fields guide migration of epidermal stem cells and promote skin wound healing
AU - Li, Li
AU - Gu, Wei
AU - Du, Juan
AU - Reid, Brian
AU - Deng, Xianjian
AU - Liu, Zhidai
AU - Zong, Zhaowen
AU - Wang, Haiyan
AU - Yao, Bo
AU - Yang, Ce
AU - Yan, Jun
AU - Zeng, Ling
AU - Chalmers, Laura
AU - Zhao, Min
AU - Jiang, Jianxin
PY - 2012/11
Y1 - 2012/11
N2 - Migration of epidermal stem cells (EpSCs) into wounds may play an important role in wound healing. Endogenous electric fields (EFs) arise naturally at wounds. Consistent with previous reports, we measured outward electric currents at rat skin wounds using vibrating probes. Topical use of prostaglandin E2 significantly promoted wound healing. However, it is not known whether EpSCs respond to EFs. We first isolated and characterized EpSCs from rat skin. We then demonstrated that EpSCs isolated from the epidermis migrated directionally toward the cathode in EFs of 50-400 mV/mm. The directedness values increased in a dose- and time-dependent fashion. The migration speed of EpSCs was significantly increased in EFs. EFs induced asymmetric polymerization of intracellular F-actin and activation of the extracellular signal-regulated kinase 1/2 and phosphatidylinositol-3-kinase (PI3K)/protein kinase B pathways. Inhibition of epidermal growth factor receptor, extracellular signal-regulated kinase 1/2, or PI3K significantly inhibited the cathodal distribution of F-actin and the electrotactic response of EpSCs. These data for the first time show that EpSCs possess obvious electrotaxis, in which the epidermal growth factor receptor-mitogen activated protein kinase-PI3K pathways are involved. These data thus suggest a novel aspect of electric signaling in wound healingâto stimulate and guide migration of EpSCs and to regulate wound healing.
AB - Migration of epidermal stem cells (EpSCs) into wounds may play an important role in wound healing. Endogenous electric fields (EFs) arise naturally at wounds. Consistent with previous reports, we measured outward electric currents at rat skin wounds using vibrating probes. Topical use of prostaglandin E2 significantly promoted wound healing. However, it is not known whether EpSCs respond to EFs. We first isolated and characterized EpSCs from rat skin. We then demonstrated that EpSCs isolated from the epidermis migrated directionally toward the cathode in EFs of 50-400 mV/mm. The directedness values increased in a dose- and time-dependent fashion. The migration speed of EpSCs was significantly increased in EFs. EFs induced asymmetric polymerization of intracellular F-actin and activation of the extracellular signal-regulated kinase 1/2 and phosphatidylinositol-3-kinase (PI3K)/protein kinase B pathways. Inhibition of epidermal growth factor receptor, extracellular signal-regulated kinase 1/2, or PI3K significantly inhibited the cathodal distribution of F-actin and the electrotactic response of EpSCs. These data for the first time show that EpSCs possess obvious electrotaxis, in which the epidermal growth factor receptor-mitogen activated protein kinase-PI3K pathways are involved. These data thus suggest a novel aspect of electric signaling in wound healingâto stimulate and guide migration of EpSCs and to regulate wound healing.
UR - http://www.scopus.com/inward/record.url?scp=84868534627&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84868534627&partnerID=8YFLogxK
U2 - 10.1111/j.1524-475X.2012.00829.x
DO - 10.1111/j.1524-475X.2012.00829.x
M3 - Article
C2 - 23082865
AN - SCOPUS:84868534627
VL - 20
SP - 840
EP - 851
JO - Wound Repair and Regeneration
JF - Wound Repair and Regeneration
SN - 1067-1927
IS - 6
ER -