Metformin Inhibits Cyst Formation in a Zebrafish Model of Polycystin-2 Deficiency

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 effectivene...

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Autores principales:	Ming-Yang Chang, Tsu-Lin Ma, Cheng-Chieh Hung, Ya-Chung Tian, Yung-Chang Chen, Chih-Wei Yang, Yi-Chuan Cheng
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7b073746b7fe4a018b85d35f2d1d0e2b
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spelling	oai:doaj.org-article:7b073746b7fe4a018b85d35f2d1d0e2b2021-12-02T15:06:21ZMetformin Inhibits Cyst Formation in a Zebrafish Model of Polycystin-2 Deficiency10.1038/s41598-017-07300-x2045-2322https://doaj.org/article/7b073746b7fe4a018b85d35f2d1d0e2b2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07300-xhttps://doaj.org/toc/2045-2322Abstract 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.Ming-Yang ChangTsu-Lin MaCheng-Chieh HungYa-Chung TianYung-Chang ChenChih-Wei YangYi-Chuan ChengNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ming-Yang Chang Tsu-Lin Ma Cheng-Chieh Hung Ya-Chung Tian Yung-Chang Chen Chih-Wei Yang Yi-Chuan Cheng Metformin Inhibits Cyst Formation in a Zebrafish Model of Polycystin-2 Deficiency
description	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.
format	article
author	Ming-Yang Chang Tsu-Lin Ma Cheng-Chieh Hung Ya-Chung Tian Yung-Chang Chen Chih-Wei Yang Yi-Chuan Cheng
author_facet	Ming-Yang Chang Tsu-Lin Ma Cheng-Chieh Hung Ya-Chung Tian Yung-Chang Chen Chih-Wei Yang Yi-Chuan Cheng
author_sort	Ming-Yang Chang
title	Metformin Inhibits Cyst Formation in a Zebrafish Model of Polycystin-2 Deficiency
title_short	Metformin Inhibits Cyst Formation in a Zebrafish Model of Polycystin-2 Deficiency
title_full	Metformin Inhibits Cyst Formation in a Zebrafish Model of Polycystin-2 Deficiency
title_fullStr	Metformin Inhibits Cyst Formation in a Zebrafish Model of Polycystin-2 Deficiency
title_full_unstemmed	Metformin Inhibits Cyst Formation in a Zebrafish Model of Polycystin-2 Deficiency
title_sort	metformin inhibits cyst formation in a zebrafish model of polycystin-2 deficiency
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/7b073746b7fe4a018b85d35f2d1d0e2b
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Metformin Inhibits Cyst Formation in a Zebrafish Model of Polycystin-2 Deficiency

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