Related Experiment Video

Updated: Jun 1, 2026

Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium
08:46

Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium

Published on: September 1, 2015

Inhibition of the P2X7 receptor reduces cystogenesis in PKD

Ming-Yang Chang1, Jenn-Kan Lu, Ya-Chung Tian

  • 1Kidney Research Center, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.

Journal of the American Society of Nephrology : JASN
|June 4, 2011
PubMed

Insights

Blocking the P2X7 receptor significantly reduced cyst formation in a polycystic kidney disease zebrafish model. This suggests P2X7 antagonists may offer a potential therapy for autosomal dominant polycystic kidney disease (ADPKD).

Area of Science:

  • Nephrology
  • Cell Biology
  • Pharmacology

Background:

  • Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder.
  • Purinergic signaling, involving the P2X7 receptor, is implicated in ADPKD progression.
  • Targeting P2X7 receptors may offer a novel therapeutic strategy for ADPKD.

Purpose of the Study:

  • To investigate the therapeutic potential of P2X7 receptor antagonists in a zebrafish model of ADPKD.
  • To determine the effects of P2X7 receptor modulation on cyst development and related cellular pathways.

Main Methods:

  • Utilized a zebrafish model with pkd2 knockdown to mimic polycystic kidney disease.
  • Administered P2X7 receptor antagonist (oxidized ATP [OxATP]) and agonist (BzATP) to zebrafish embryos.
  • Observed cyst development in pronephric kidneys using GFP-expressing zebrafish.
  • Assessed p-ERK activity and cell proliferation via histology and molecular analysis.

Main Results:

  • OxATP treatment significantly reduced the frequency and severity of kidney cysts in pkd2 morphants.
  • P2X7 receptor blockade decreased p-ERK activity and cell proliferation in affected kidneys.
  • Confirmation of P2X7 receptor's role through additional antagonists and gene knockdown.

Conclusions:

  • P2X7 receptor blockade effectively reduces cyst formation in a preclinical model of polycystic kidney disease.
  • The therapeutic effect is mediated through ERK-dependent pathways.
  • P2X7 receptor antagonists represent a promising therapeutic avenue for ADPKD treatment.

More Related Videos

Use of Ultra-high Field MRI in Small Rodent Models of Polycystic Kidney Disease for In Vivo Phenotyping and Drug Monitoring07:35

Use of Ultra-high Field MRI in Small Rodent Models of Polycystic Kidney Disease for In Vivo Phenotyping and Drug Monitoring

Published on: June 23, 2015

Related Concept Videos

GPCR Desensitization01:12

GPCR Desensitization

G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...