Inhibition of the P2X7 receptor reduces cystogenesis in PKD

Ming Yang Chang, Jenn Kan Lu, Ya Chung Tian, Yung Chang Chen, Cheng Chieh Hung, Yi Hui Huang, Yau Hung Chen, Mai Szu Wu, Chih Wei Yang, Yi Chuan Cheng

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1696-1706
Number of pages11
JournalJournal of the American Society of Nephrology
Volume22
Issue number9
DOIs
Publication statusPublished - Sep 2011
Externally publishedYes

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Purinergic P2X7 Receptors
Zebrafish
Autosomal Dominant Polycystic Kidney
Cysts
Morpholinos
Polycystic Kidney Diseases
Pronephros
MAP Kinase Signaling System
Histology
Embryonic Structures
Cell Proliferation
Phenotype
Kidney
Therapeutics
2',3'-dialdehyde ATP

ASJC Scopus subject areas

  • Nephrology

Cite this

Chang, M. Y., Lu, J. K., Tian, Y. C., Chen, Y. C., Hung, C. C., Huang, Y. H., ... Cheng, Y. C. (2011). Inhibition of the P2X7 receptor reduces cystogenesis in PKD. Journal of the American Society of Nephrology, 22(9), 1696-1706. https://doi.org/10.1681/ASN.2010070728

Inhibition of the P2X7 receptor reduces cystogenesis in PKD. / 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.

In: Journal of the American Society of Nephrology, Vol. 22, No. 9, 09.2011, p. 1696-1706.

Research output: Contribution to journalArticle

Chang, MY, Lu, JK, Tian, YC, Chen, YC, Hung, CC, Huang, YH, Chen, YH, Wu, MS, Yang, CW & Cheng, YC 2011, 'Inhibition of the P2X7 receptor reduces cystogenesis in PKD', Journal of the American Society of Nephrology, vol. 22, no. 9, pp. 1696-1706. https://doi.org/10.1681/ASN.2010070728
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. / Inhibition of the P2X7 receptor reduces cystogenesis in PKD. In: Journal of the American Society of Nephrology. 2011 ; Vol. 22, No. 9. pp. 1696-1706.
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