The role of electrical signals in murine corneal wound re-epithelialization.

The role of electrical signals in murine corneal wound re-epithelialization.
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DOI:
10.1002/jcp.22488
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发表时间:
2011-06
影响因子:
5.6
通讯作者:
Collinson, J. Martin
Collinson, J. Martin
中科院分区:
生物学2区
文献类型:
--
作者:
Kucerova, Romana;Walczysko, Petr;Reid, Brian;Ou, Jingxing;Leiper, Lucy J.;Rajnicek, Ann M.;Mccaig, Colin D.;Zhao, Min;Collinson, J. Martin

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从完整组织进入上皮伤口部位的离子流导致横向电流,其可能代表伤口愈合细胞迁移的主要驱动力。使用外加电场促进伤口愈合是Medicare批准的电刺激疗法的基础。本研究使用人眼表异常无虹膜角膜病变(其中伤口愈合和角膜上皮细胞迁移被破坏)的Pax 6 +/−小鼠模型,研究了电场在伤口上皮再生中的作用。野生型和Pax 6 +/−角膜上皮细胞在体外对外加电场的反应中表现出迁移速度增加。然而,只有Pax 6 +/+细胞表现出对阴极的定向趋电性,pSrc信号的激活,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Pax 6 +/−角膜表现出逆转的内源性伤口诱导电流(伤口是阳极)。这些角膜的愈合速度与野生型相同。令人惊讶的是,上皮细胞迁移与野生型或突变型角膜的内源性电流的方向或幅度无关。此外,在体内愈合期间,没有观察到pSrc的极化。我们发现很少有证据表明,Src依赖的细胞迁移机制,观察到在体外应用EF,通常存在于体内。可以得出结论,内源性电场不驱动长期方向性的持续愈合迁移在这个小鼠角膜上皮模型。然而,来自伤口的离子流可能代表伤口信号传导起始的重要组成部分。
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 to promote wound healing is the basis of Medicare-approved electric stimulation therapy. This study investigated the roles for electric fields in wound re-epithelialisation, 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 and Pax6+/− corneal epithelial cells showed increased migration speeds in response to applied electric fields in vitro. However, only Pax6+/+ cells demonstrated directional galvanotaxis towards the cathode, with activation of pSrc signalling, polarised 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 wild-type. Surprisingly, epithelial migration did not correlate with direction or magnitude of endogenous currents for wild-type or mutant corneas. Furthermore, during healing in vivo, no polarisation 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 electric fields 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 signalling initiation.
DOI: 10.1152/ajpregu.1982.242.3.r358
发表时间: 1982-01-01
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发表时间: 2008-05
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