Shotokuseki Extract Promotes Keratinocyte Differentiation Even at a Low Calcium Concentration

Abstract

The switch between keratinocyte proliferation and differentiation is regulated by extracellular calcium levels, requiring high concentrations (>1 mol/L) of extracellular calcium to induce differentiation. The Shotokuseki extract (SE) contains various ions such as calcium, but its effect on keratinocytes is unknown. This study focused on calcium-induced differentiation of keratinocytes and investigated the effects of simultaneous application of calcium and other ions on keratinocyte differentiation. The expression of differentiation markers increased when SE was added to a keratinocyte culture but not when only calcium was added at the same concentration present in SE. The calcium concentration in SE was found to be too low (0.01 mol/L) to induce differentiation of keratinocytes. In addition, the application of SE increased intracellular calcium concentration compared with calcium solution alone. Therefore, the induction of keratinocyte differentiation by SE is not calcium-dependent, or SE may alter the calcium sensitivity of keratinocytes. In our study, we found that simultaneous application of multiple ions and/or the application of trace ions may alter calcium sensitivity and the epidermal cell response. The function of ion transporters associated with these ions and the response of cells to ions depends largely on the balance among various ions and the function of trace ions.