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

doi:10.1681/ASN.2010070728

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 journal › Article › peer-review

46 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 language	English
Pages (from-to)	1696-1706
Number of pages	11
Journal	Journal of the American Society of Nephrology
Volume	22
Issue number	9
DOIs	https://doi.org/10.1681/ASN.2010070728
Publication status	Published - Sept 2011
Externally published	Yes

ASJC Scopus subject areas

General Medicine

Access to Document

10.1681/ASN.2010070728

Cite this

@article{8c11f54ef0fa46a38836477ec4309491,

title = "Inhibition of the P2X7 receptor reduces cystogenesis in PKD",

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.",

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

year = "2011",

month = sep,

doi = "10.1681/ASN.2010070728",

language = "English",

volume = "22",

pages = "1696--1706",

journal = "Journal of the American Society of Nephrology",

issn = "1046-6673",

publisher = "American Society of Nephrology",

number = "9",

}

TY - JOUR

T1 - Inhibition of the P2X7 receptor reduces cystogenesis in PKD

AU - Chang, Ming Yang

AU - Lu, Jenn Kan

AU - Tian, Ya Chung

AU - Chen, Yung Chang

AU - Hung, Cheng Chieh

AU - Huang, Yi Hui

AU - Chen, Yau Hung

AU - Wu, Mai Szu

AU - Yang, Chih Wei

AU - Cheng, Yi Chuan

PY - 2011/9

Y1 - 2011/9

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=80052341827&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052341827&partnerID=8YFLogxK

U2 - 10.1681/ASN.2010070728

DO - 10.1681/ASN.2010070728

M3 - Article

C2 - 21636640

AN - SCOPUS:80052341827

SN - 1046-6673

VL - 22

SP - 1696

EP - 1706

JO - Journal of the American Society of Nephrology

JF - Journal of the American Society of Nephrology

IS - 9

ER -

Inhibition of the P2X7 receptor reduces cystogenesis in PKD

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this