Hillman Katherine A, Johnson Tanya M, Winyard Paul J D, Burnstock Geoffrey, Unwin Robert J, Woolf Adrian S
Centre for Nephrology, Institute of Urology and Nephrology, Middlesex Hospital, University College London, London, UK.
Exp Nephrol. 2002;10(1):34-42. doi: 10.1159/000049896.
Purinergic receptors are cell-surface molecules that bind extracellular nucleotides, notably ATP. The P2X family includes seven nonselective ion channels with one member, P2X(7), implicated in cytolytic pore formation and cell death.
We sought P2X(7) expression in mouse nephrogenesis and cpk/cpk renal cyst growth, conditions in which both proliferation and apoptosis are prominent.
P2X(7) 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, P2X(7) was detected in collecting ducts, a pattern persisting to maturity. A mesenchymal to epithelial shift of P2X(7) expression was also documented in ureter development. In cpk/cpk kidneys, P2X(7)-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 P2X(7)-expressing epithelia, but were detected between cysts, consistent with a non-apoptotic role for P2X(7) in cyst enlargement.
P2X(7) is expressed during normal nephrogenesis and in a model of congenital polycystic kidney disease. Further experiments are necessary to define possible functions of P2X(7) in these settings.
嘌呤能受体是结合细胞外核苷酸(尤其是ATP)的细胞表面分子。P2X家族包括七个非选择性离子通道,其中一个成员P2X(7)与溶细胞性孔形成和细胞死亡有关。
我们研究了P2X(7)在小鼠肾发生以及cpk/cpk肾囊肿生长过程中的表达情况,在这些过程中增殖和凋亡都很显著。
P2X(7)免疫定位到浓缩的后肾间充质:通过增殖细胞核抗原表达和碘化丙啶染色的固缩核分别评估,在这个区域检测到了增殖和凋亡。在肾发生后期,在集合管中检测到P2X(7),这种模式持续到成熟。在输尿管发育过程中也记录到了P2X(7)表达的间充质到上皮的转变。在cpk/cpk肾中,表达P2X(7)的集合管囊肿在出生后两周直至四周的组织学中占主导地位,此时动物死于尿毒症。在多囊肾中,在表达P2X(7)的上皮细胞中很少发现固缩核,但在囊肿之间检测到了,这与P2X(7)在囊肿扩大中起非凋亡作用一致。
P2X(7)在正常肾发生过程以及先天性多囊肾病模型中表达。需要进一步的实验来确定P2X(7)在这些情况下的可能功能。