School of Medical Sciences, Institute of Medical Sciences Foresterhill, University of Aberdeen, Aberdeen AB25 2ZD, UK.
J Cell Physiol. 2011 Jun;226(6):1544-53. doi: 10.1002/jcp.22488.
Ion flow from intact tissue into epithelial wound sites results in lateral electric currents that may represent a major driver of wound healing cell migration. Use of applied electric fields (EF) to promote wound healing is the basis of Medicare-approved electric stimulation therapy. This study investigated the roles for EFs in wound re-epithelialization, using the Pax6(+/-) mouse model of the human ocular surface abnormality aniridic keratopathy (in which wound healing and corneal epithelial cell migration are disrupted). Both wild-type (WT) and Pax6(+/-) corneal epithelial cells showed increased migration speeds in response to applied EFs in vitro. However, only Pax6(+/+) cells demonstrated consistent directional galvanotaxis towards the cathode, with activation of pSrc signaling, polarized to the leading edges of cells. In vivo, the epithelial wound site normally represents a cathode, but 43% of Pax6(+/-) corneas exhibited reversed endogenous wound-induced currents (the wound was an anode). These corneas healed at the same rate as WT. Surprisingly, epithelial migration did not correlate with direction or magnitude of endogenous currents for WT or mutant corneas. Furthermore, during healing in vivo, no polarization of pSrc was observed. We found little evidence that Src-dependent mechanisms of cell migration, observed in response to applied EFs in vitro, normally exist in vivo. It is concluded that endogenous EFs do not drive long-term directionality of sustained healing migration in this mouse corneal epithelial model. Ion flow from wounds may nevertheless represent an important component of wound signaling initiation.
完整组织中的离子流进入上皮伤口部位会产生横向电流，这可能代表伤口愈合细胞迁移的主要驱动力。应用电场 (EF) 促进伤口愈合是医疗保险批准的电刺激治疗的基础。本研究使用 Pax6( +/- ) 小鼠模型（一种人类眼表面异常无虹膜角膜病变，其中伤口愈合和角膜上皮细胞迁移受到干扰）研究了 EF 在伤口再上皮化中的作用。野生型 (WT) 和 Pax6( +/- ) 角膜上皮细胞在体外对施加的 EF 均表现出迁移速度增加。然而，只有 Pax6( + / + ) 细胞表现出一致的向阴极的定向电趋化性，同时激活了 pSrc 信号，极化到细胞的前缘。在体内，上皮伤口部位通常代表阴极，但 43%的 Pax6( +/- ) 角膜表现出相反的内源性伤口诱导电流（伤口为阳极）。这些角膜的愈合速度与 WT 相同。令人惊讶的是，上皮迁移与 WT 或突变角膜的内源性电流的方向或大小无关。此外，在体内愈合过程中，未观察到 pSrc 的极化。我们发现很少有证据表明，在体外应用 EF 时观察到的 Src 依赖性细胞迁移机制在体内正常存在。结论是，内源性 EF 不会驱动这种小鼠角膜上皮模型中持续愈合迁移的长期方向性。然而，伤口处的离子流可能仍然代表伤口信号起始的重要组成部分。
