Michael Stern Translational Laboratory for Polycystic Kidney Disease, Centre for Transplant and Renal Research, Westmead Millennium Institute, University of Sydney Sydney, NSW, Australia.
Front Physiol. 2013 Aug 16;4:218. doi: 10.3389/fphys.2013.00218. eCollection 2013.
Polycystic kidney diseases (PKD) are a group of inherited ciliopathies in which the formation and growth of multiple cysts derived from the distal nephron and collecting duct leads to the disruption of normal kidney architecture, chronic interstitial inflammation/fibrosis and hypertension. Kidney failure is the most life-threatening complication of PKD, and is the consequence of cyst expansion, renal interstitial disease and loss of normal kidney tissue. Over the last decade, accumulating evidence suggests that the autocrine and paracrine effects of ATP (through its receptor family P2X and P2Y), could be detrimental for the progression of PKD. (2009). In vitro, ATP-P2 signaling promotes cystic epithelial cell proliferation, chloride-driven fluid secretion and apoptosis. Furthermore, dysfunction of the polycystin signal transduction pathways promotes the secretagogue activity of extracellular ATP by activating a calcium-activated chloride channel via purinergic receptors. Finally, ATP is a danger signal and could potentially contribute to interstitial inflammation associated with PKD. These data suggest that ATP-P2 signaling worsens the progression of cyst enlargement and interstitial inflammation in PKD.
多囊肾病（PKD）是一组遗传性纤毛病，其中来源于远端肾单位和集合管的多个囊肿的形成和生长导致正常肾脏结构的破坏、慢性间质炎症/纤维化和高血压。肾衰竭是 PKD 最具威胁生命的并发症，是囊肿扩张、肾间质疾病和正常肾组织丧失的结果。在过去的十年中，越来越多的证据表明，ATP 的自分泌和旁分泌作用（通过其受体家族 P2X 和 P2Y）可能对 PKD 的进展有害。（2009 年）。在体外，ATP-P2 信号促进囊性上皮细胞增殖、氯离子驱动的液体分泌和细胞凋亡。此外，多囊蛋白信号转导通路的功能障碍通过嘌呤能受体激活钙激活氯离子通道来促进细胞外 ATP 的分泌活性。最后，ATP 是一种危险信号，可能与 PKD 相关的间质炎症有关。这些数据表明，ATP-P2 信号会加重 PKD 中囊肿增大和间质炎症的进展。
