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    题名: Inhibition of the P2X7 Receptor Reduces Cystogenesis in PKD
    作者: Chang, Ming-yang;Lu, Jenn-kan;Tian, Ya-chung;Chen, Yung-chang;Hung, Cheng-chieh;Huang, Yi-hui;Chen, Yau-hung;Wu, Mai-szu;Yang, Chih-wei;Cheng, Yi-chuan
    贡献者: 淡江大學化學學系
    日期: 2011-09
    上传时间: 2012-05-24 11:15:43 (UTC+8)
    出版者: Washington: American Society of Nephrology
    摘要: The P2X7 receptor participates in purinergic signaling, which may promote the progression of ADPKD. We examined the effects of a P2X7 receptor antagonist and a P2X7 receptor agonist on cyst development in a zebrafish model of polycystic kidney disease in which we knocked down pkd2 by morpholinos. We used live wt-1b pronephric-specific GFP-expressing zebrafish embryos to directly observe changes in the pronephros. Exposure of pkd2-morphant zebrafish to a P2X7 receptor antagonist (oxidized ATP [OxATP]) significantly reduced the frequency of the cystic phenotype compared with either exposure to a P2X7 receptor agonist (BzATP) or with no treatment (P < 0.01). Histology confirmed improvement of glomerular cysts in OxATP-treated pkd2 morphants. OxATP also reduced p-ERK activity and cell proliferation in pronephric kidneys in pkd2 morphants. Inhibition of P2X7 with an additional specific antagonist (A-438079), and through morpholino-mediated knockdown of p2rx7, confirmed these effects. In conclusion, blockade of the P2X7 receptor reduces cyst formation via ERK-dependent pathways in a zebrafish model of polycystic kidney disease, suggesting that P2X7 antagonists may have therapeutic potential in ADPKD.
    關聯: Journal of the American Society of Nephrology 22(9), pp.1696-1706
    DOI: 10.1681/ASN.2010070728
    显示于类别:[生命科學研究所] 期刊論文

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