The P2X₇ ATP receptor modulates renal cyst development in vitro

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• 作者：Hillman ; Kate A. ; Woolf ; Adrian S. ; Johnson ; Tanya M. ; Wade ; Angela ; Unwin ; Robert J. ; Winyard ; Paul J.D.
• 关键词：Cell culture ; Cyst ; Epithelium ; Kidney ; Purinergic ; P2X₇
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2004
• 出版时间：September 17, 2004
• 年：2004
• 卷：322
• 期：2
• 页码：434-439
• 全文大小：1007 K

文摘

P2X₇, a purinergic receptor, is expressed in renal collecting ducts as they undergo fulminant cystogenesis in the cpk/cpk mouse model of autosomal recessive polycystic kidney disease (ARPKD). Dissociated cpk/cpk kidneys generate cysts from cell aggregates within 24h of suspension culture and we demonstrate that BzATP, a P2X₇ agonist, reduces cystogenesis. This effect is P2X₇-specific, because: (i) equimolar concentrations of other purinergic agonists, ATP and UTP, had lesser effects and (ii) the P2X₇ inhibitor, oxidized ATP, abrogated the BzATP-mediated reduction in cystogenesis. BzATP did not significantly affect total cell number, proliferation, LDH release or caspase 3 activity, and zVAD-fmk, a caspase blocker, failed to modulate BzATP effects. In addition, this P2X₇ agonist did not significantly alter cyst size, probably excluding altered vectorial transport. In vivo, ATP was detected in cyst fluid from cpk/cpk kidneys; moreover, P2X₇ protein was also upregulated in human fetal ARPKD epithelia versus normal fetal collecting ducts. Thus, ATP may inhibit pathological renal cyst growth through P2X₇ signaling.