Abstract
Restoration of proximal tubular cell integrity and function after ischemic injury involves cell migration and proliferation. Endogenous fields are present during embryonic development and wound healing. Electric field (EF)-induced effects on cell migration have been observed in many cell types. This study investigated the effect of physiological direct current EF (dc EF) on the motility of renal epithelial cells. Human renal tubular epithelial (HK-2) and human-derived renal epithelial (HEK-293) cells were exposed to dc EF at physiological magnitude. Cell images were recorded and analyzed using an image analyzer. Cell lysates were used to detect protein expression by western blot. Scratch wounds were created in monolayers of HK-2 cells, and wound areas of cells were measured in response to EF exposure. Cells migrated significantly faster in the presence of an EF and toward the cathode. Application of an EF led to activation of the Erk1/2, p38 MAPK, and Akt signaling pathways. Pharmacological inhibition of Erk1/2, p38 MAPK, and Akt impaired EF-induced migratory responses, such as motility rate and directedness. In addition, exposure of the monolayers to EF enhanced EF-induced HK-2 wound healing. Our results suggest that EFs augment the rate of single renal epithelium migration and induce cell cathodal migration through activation of Erk1/2, p38 MAPK, and Akt signaling. Moreover, exposure of the renal epithelium to EF facilitated closure of in vitro small wounds by enhancing cell migration.
Highlights
Cell migration, including epithelial cell migration, is a key component of normal tissue homeostasis but is crucial for wound healing and tissue regeneration (Aman and Piotrowski, 2010; Calve and Simon, 2012)
We provide evidence that electric field (EF) markedly induces the migration of human renal epithelial cells, which extends our knowledge concerning EF-responsive cell types (McCaig and Zhao, 1997)
We demonstrated that renal epithelial cells migrated significantly faster in the presence of an EF and toward the cathode
Summary
Cell migration, including epithelial cell migration, is a key component of normal tissue homeostasis but is crucial for wound healing and tissue regeneration (Aman and Piotrowski, 2010; Calve and Simon, 2012). Studies have shown that the migration of a variety of cells, such as neural crest cells (Nuccitelli and Erickson, 1983; Stump and Robinson, 1983), fibroblasts (Erickson and Nuccitelli, 1984), neurons (Jaffe and Poo, 1979; Hinkle et al, 1981), endothelial cells (Bai et al, 2004; Zhao et al, 2004), and corneal epithelial cells (Soong et al, 1990), originating from different organs can be guided by an applied EF These results indicate the possibility that EFs may direct renal epithelial cells to migrate in vivo and have implications for use in acute kidney lesions to initiate the tubular regeneration process. It is critical to elucidate the potential mechanisms underlying this behavior
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