P2X ₇ Receptors Are Expressed during Mouse Nephrogenesis and in Collecting Duct Cysts of the cpk/cpk Mouse

Abstract

Background: Purinergic receptors are cell-surface molecules that bind extracellular nucleotides, notably ATP. The P2X family includes seven nonselective ion channels with one member, P2X₇, implicated in cytolytic pore formation and cell death. Materials and Methods: We sought P2X₇ expression in mouse nephrogenesis and cpk/cpk renal cyst growth, conditions in which both proliferation and apoptosis are prominent. Results: P2X₇ immunolocalized to condensed metanephric mesenchyme: both proliferation and apoptosis were detected in this compartment, assessed by proliferating cell nuclear antigen expression and propidium iodide-stained pyknotic nuclei respectively. Later in nephrogenesis, P2X₇ was detected in collecting ducts, a pattern persisting to maturity. A mesenchymal to epithelial shift of P2X₇ expression was also documented in ureter development. In cpk/cpk kidneys, P2X₇-expressing collecting duct cysts dominated histology from two weeks until four weeks after birth, when animals die from uremia. In polycystic kidneys pyknotic nuclei were rarely identified in P2X₇-expressing epithelia, but were detected between cysts, consistent with a non-apoptotic role for P2X₇ in cyst enlargement. Conclusion: P2X₇ is expressed during normal nephrogenesis and in a model of congenital polycystic kidney disease. Further experiments are necessary to define possible functions of P2X₇ in these settings.