Purinergic receptors are part of a signaling system for keratinocyte proliferation, differentiation, and apoptosis in human fetal epidermis

We have investigated the expression of P2X(5), P2X(7), P2Y(1), and P2Y(2) receptor subtypes in 8- to 11-wk-old human fetal epidermis in relation to markers of pro-liferation (proliferating cell nuclear antigen (PCNA) and Ki-67), keratinocyte differentiation (cytokeratin K10 and involucrin), and markers of apoptosis (TdT-mediated dUTP nick end labeling (TUNEL) and anti-caspase-3). Immunohistochemistry showed that each of the four receptors was expressed in spatially distinct zones of the developing epidermis: P2Y(1) receptors were found in the basal layer, P2X(5) receptors were predominantly in the basal and intermediate layers, and both P2Y(2) and P2X(7) receptors were in the periderm. Colo-calization experiments suggested different functional roles for these receptors. P2Y(1) receptors were found in fetal keratinocytes positive for PCNA and Ki-67, suggesting a role in proliferation. P2X(5) receptors double labeled with differentiated fetal keratinocytes that were positive for cytokeratin K10, suggesting a role in differentiation. P2X(7) receptors colocalized with anti-caspase-3 antibody and were also expressed in periderm cells positive for TUNEL, suggesting a role in periderm cell apoptosis. P2Y(2) receptors were found only in periderm cells and may have a role in chloride and fluid secretion into the amniotic fluid.