Abstract
Keratinocyte migration is initiated toward the wound skin barrier as a crucial process in wound healing. However, the migratory machinery used by keratinocytes is relatively unknown. Histamine signaling, including an increase in the Ca2+ signal, mediated the enhanced protein expression and chloride/bicarbonate exchange activity of anion exchanger AE2 in keratinocytes. In this study, we applied an agarose spot assay to induce a vectorial motion. The vectorial stimulation of the histamine-containing agarose spot enhanced the HaCaT keratinocyte migration, compared to non-directional stimulation. AE2 is associated with the vectorial movement of HaCaT keratinocytes. Enhanced expression of AE2 was mainly associated with an increase in Ca2+ and was abolished by the treatment with the Ca2+ chelating agent BAPTA-AM. These findings revealed that the directionality of Ca2+-exerted stimulation can play a prominent role in facilitating migration through the involvement of AE2 as a migratory machinery in HaCaT keratinocytes.
Highlights
The skin barrier is the first defense barrier that protects the body from exogenous stimuli
These results suggest that histamine stimulation enhanced AE2 expression and chloride bicarbonate exchanger (CBE) activity in keratinocytes
The increase of Ca2+ by inflammatory mediators, such as histamine, enhanced AE2 expression, and activity in keratinocytes. Both AE2 and AE3 were expressed in HaCaT cells, AE2 was statistically enhanced by the histamine stimulation
Summary
The skin barrier is the first defense barrier that protects the body from exogenous stimuli. The expression of AE2 is involved in the maintenance of the intracellular pH through the exchange of bicarbonate ions [5,6]. In addition to the classical role of bicarbonate transporters in the cellular pH maintenance, cell volume regulation is a dominant function of these transporters for cellular migration [7]. The precise role of inflammatory mediators or of the involvement of their subsequent inflammatory Ca2+ signaling and transporters in migratory machinery still need to be determined. The expression or function of AE in keratinocyte migration has not been elucidated from a migratory machinery perspective. Cellular migration or invasion is mediated by migratory machinery through the involvement of ion transporters and exchangers [16]. We hypothesized that involvement of bicarbonate transporters is crucial for regulating the migratory machinery of keratinocytes
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