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Updated: Feb 25, 2026
A Possible Zebrafish Model of Polycystic Kidney Disease: Knockdown of wnt5a Causes Cysts in Zebrafish Kidneys
Published on: December 2, 2014
Metformin Inhibits Cyst Formation in a Zebrafish Model of Polycystin-2 Deficiency
Ming-Yang Chang1, Tsu-Lin Ma1, Cheng-Chieh Hung1
1Kidney Research Center and Department of Nephrology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Abstract:
Autosomal dominant polycystic kidney disease (ADPKD) is a common kidney disease caused by mutations in PKD1 or PKD2. Metformin reduces cyst growth in mouse models of PKD1. However, metformin has not been studied in animal models of PKD2, and the cellular mechanism underlying its effectiveness is not entirely clear. This study investigated the effects of metformin on cyst formation in a zebrafish model of polycystin-2 deficiency resulting from morpholino knockdown of pkd2. We added metformin (2.5 to 20 mM) to the embryo media between 4 and 48 hours post fertilisation and observed pronephric cyst formation by using the wt1b promoter-driven GFP signal in Tg(wt1b:GFP) pkd2 morphants. Metformin inhibited pronephric cyst formation by 42-61% compared with the untreated controls. Metformin also reduced the number of proliferating cells in the pronephric ducts, the degree of dorsal body curvature, and the infiltration of leukocytes surrounding the pronephros. Moreover, metformin treatment increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and enhanced autophagy in the pronephros. Our data suggest that metformin reduces cyst formation through activation of the AMPK pathway and modulation of defective cellular events such as proliferation and autophagy. These results also imply that metformin could have therapeutic potential for ADPKD treatment.
Insights
Metformin effectively reduced cyst growth in a zebrafish model of polycystic kidney disease (PKD) linked to polycystin-2 deficiency. This suggests metformin may be a potential treatment for autosomal dominant polycystic kidney disease (ADPKD).
Area of Science:
- Nephrology
- Genetics
- Pharmacology
Background:
- Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic kidney disorder.
- Mutations in PKD1 or PKD2 cause ADPKD, leading to cyst formation.
- Metformin shows promise in PKD1 mouse models, but its effect on PKD2 deficiency is unknown.
Purpose of the Study:
- To investigate the therapeutic potential of metformin in a zebrafish model of polycystin-2 deficiency.
- To elucidate the cellular mechanisms by which metformin affects cystogenesis in PKD.
Main Methods:
- A zebrafish model (Tg(wt1b:GFP) pkd2 morphants) was used to study polycystin-2 deficiency.
- Metformin was administered to embryos from 4 to 48 hours post-fertilization.
- Pronephric cyst formation, cell proliferation, body curvature, leukocyte infiltration, AMPK phosphorylation, and autophagy were assessed.
Main Results:
- Metformin significantly inhibited pronephric cyst formation (42-61%) in pkd2 morphants.
- Treatment reduced cell proliferation, dorsal body curvature, and leukocyte infiltration.
- Metformin increased AMPK phosphorylation and enhanced autophagy in the pronephros.
Conclusions:
- Metformin reduces cyst formation in a zebrafish model of polycystin-2 deficiency.
- The drug acts by activating the AMPK pathway and modulating proliferation and autophagy.
- These findings suggest metformin as a potential therapeutic agent for ADPKD.
