Directed migration, re-orientation and inhibited proliferation of lens epithelial cells in applied electric fields
Physiological electric fields (EFs) exist in the vertebrate lens, but the importance of the endogenous EF is not well understood yet. In the present study, an applied EF to mimic endogenous EFs was applied to cultured lens epithelial cells (LECs) to investigate the effects of EFs on the behaviours of LECs and the underlying mechanisms. It was showed that LEG migration was directed and migration rate was increased in applied EFs, and serum or growth factors were required for these EF-induced cell responses. LECs elongated and re-oriented to lie perpendicular to field vector. Healing of LEG monolayer wounds was also influenced by EF polarity. EF exposure enhanced the activation of extracellular signal-regulated kinase (ERK) ½ and induced an asymmetric distribution of active ERK ½ in monolayer wounds. Mitogen-activated protein (MAP) kinase inhibitor U0126 inhibited the directed migration and reorientation of LECs in EFs and the healing of LEG monolayer wound, and U0126 also completely prevented activation of ERK ½ in LECs. It is suggested that MAP kinase signaling pathways were involved in the responses of LECs to EF stimulation. EF exposure also inhibited the proliferation of the LECs. Cell cycle analysis showed that EF exposure inhibited the Gl/S transition of the cell cycle progression in LECs, resulting in a Gl-block. The EF-induced down-regulated expression of Gl-specific cell cycle protein cyclin E and the up-regulated expression of cyclin-Cdk (cycle dependent kinase) complex inhibitor p27 kipl were accounted for the cell cycle arrest of LECs in EFs. This study implies that a physiological EF may be one of the guidance cues regulating LEG behaviours in vivo and applying EFs may be one way of controlling aberrant LEG behaviours in vitro and in vivo.