PUBLICATION
Metformin Inhibits Cyst Formation in a Zebrafish Model of Polycystin-2 Deficiency
- Authors
- Chang, M.Y., Ma, T.L., Hung, C.C., Tian, Y.C., Chen, Y.C., Yang, C.W., Cheng, Y.C.
- ID
- ZDB-PUB-170805-18
- Date
- 2017
- Source
- Scientific Reports 7: 7161 (Journal)
- Registered Authors
- Keywords
- Development, Polycystic kidney disease
- MeSH Terms
-
- AMP-Activated Protein Kinases/metabolism
- Animals
- Autophagy/drug effects
- Autophagy/genetics
- Cell Proliferation/drug effects
- Cloaca/abnormalities
- Cysts/drug therapy
- Cysts/etiology
- Cysts/pathology*
- Disease Models, Animal
- Kidney Tubules/cytology
- Leukocytes/drug effects
- Leukocytes/metabolism
- Metformin/pharmacology*
- Polycystic Kidney, Autosomal Dominant/drug therapy
- Polycystic Kidney, Autosomal Dominant/genetics*
- Polycystic Kidney, Autosomal Dominant/metabolism
- Polycystic Kidney, Autosomal Dominant/pathology*
- Spinal Curvatures/drug therapy
- TRPP Cation Channels/deficiency*
- TRPP Cation Channels/genetics
- TRPP Cation Channels/metabolism
- Zebrafish
- PubMed
- 28769124 Full text @ Sci. Rep.
Citation
Chang, M.Y., Ma, T.L., Hung, C.C., Tian, Y.C., Chen, Y.C., Yang, C.W., Cheng, Y.C. (2017) Metformin Inhibits Cyst Formation in a Zebrafish Model of Polycystin-2 Deficiency. Scientific Reports. 7:7161.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping