PUBLICATION
Inhibition of the P2X7 Receptor Reduces Cystogenesis in PKD
- Authors
- Chang, M.Y., Lu, J.K., Tian, Y.C., Chen, Y.C., Hung, C.C., Huang, Y.H., Chen, Y.H., Wu, M.S., Yang, C.W., and Cheng, Y.C.
- ID
- ZDB-PUB-110609-54
- Date
- 2011
- Source
- Journal of the American Society of Nephrology : JASN 22(9): 1696-706 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Purinergic P2X Receptor Antagonists
- Humans
- RNA, Messenger/metabolism
- Purinergic P2X Receptor Agonists
- Receptors, Purinergic P2X7/genetics
- PubMed
- 21636640 Full text @ J. Am. Soc. Nephrol.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping