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Effect of Trehalose Supplementation on Autophagy and Cystogenesis in a Mouse Model of Polycystic Kidney Disease

Autophagy impairment has been demonstrated in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD) and could be a new target of treatment. Trehalose is a natural, nonreducing disaccharide that has been shown to enhance autophagy. Therefore, we investigated whether trehalose treat...

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Autores principales: Chou, Li-Fang, Cheng, Ya-Lien, Hsieh, Chun-Yih, Lin, Chan-Yu, Yang, Huang-Yu, Chen, Yung-Chang, Hung, Cheng-Chieh, Tian, Ya-Chung, Yang, Chih-Wei, Chang, Ming-Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356442/
https://www.ncbi.nlm.nih.gov/pubmed/30585217
http://dx.doi.org/10.3390/nu11010042
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author Chou, Li-Fang
Cheng, Ya-Lien
Hsieh, Chun-Yih
Lin, Chan-Yu
Yang, Huang-Yu
Chen, Yung-Chang
Hung, Cheng-Chieh
Tian, Ya-Chung
Yang, Chih-Wei
Chang, Ming-Yang
author_facet Chou, Li-Fang
Cheng, Ya-Lien
Hsieh, Chun-Yih
Lin, Chan-Yu
Yang, Huang-Yu
Chen, Yung-Chang
Hung, Cheng-Chieh
Tian, Ya-Chung
Yang, Chih-Wei
Chang, Ming-Yang
author_sort Chou, Li-Fang
collection PubMed
description Autophagy impairment has been demonstrated in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD) and could be a new target of treatment. Trehalose is a natural, nonreducing disaccharide that has been shown to enhance autophagy. Therefore, we investigated whether trehalose treatment reduces renal cyst formation in a Pkd1-hypomorphic mouse model. Pkd1 miRNA transgenic (Pkd1 miR Tg) mice and wild-type littermates were given drinking water supplemented with 2% trehalose from postnatal day 35 to postnatal day 91. The control groups received pure water or 2% sucrose for the control of hyperosmolarity. The effect on kidney weights, cystic indices, renal function, cell proliferation, and autophagic activities was determined. We found that Pkd1 miR Tg mice had a significantly lower renal mRNA expression of autophagy-related genes, including atg5, atg12, ulk1, beclin1, and p62, compared with wild-type control mice. Furthermore, immunohistochemical analysis showed that cystic lining cells had strong positive staining for the p62 protein, indicating impaired degradation of the protein by the autophagy-lysosome pathway. However, trehalose treatment did not improve reduced autophagy activities, nor did it reduce relative kidney weights, plasma blood urea nitrogen levels, or cystatin C levels in Pkd1 miR Tg mice. Histomorphological analysis revealed no significant differences in the renal cyst index, fibrosis score, or proliferative score among trehalose-, sucrose-, and water-treated groups. Our results demonstrate that adding trehalose to drinking water does not modulate autophagy activities and renal cystogenesis in Pkd1-deficient mice, suggesting that an oral supplement of trehalose may not affect the progression of ADPKD.
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spelling pubmed-63564422019-02-01 Effect of Trehalose Supplementation on Autophagy and Cystogenesis in a Mouse Model of Polycystic Kidney Disease Chou, Li-Fang Cheng, Ya-Lien Hsieh, Chun-Yih Lin, Chan-Yu Yang, Huang-Yu Chen, Yung-Chang Hung, Cheng-Chieh Tian, Ya-Chung Yang, Chih-Wei Chang, Ming-Yang Nutrients Article Autophagy impairment has been demonstrated in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD) and could be a new target of treatment. Trehalose is a natural, nonreducing disaccharide that has been shown to enhance autophagy. Therefore, we investigated whether trehalose treatment reduces renal cyst formation in a Pkd1-hypomorphic mouse model. Pkd1 miRNA transgenic (Pkd1 miR Tg) mice and wild-type littermates were given drinking water supplemented with 2% trehalose from postnatal day 35 to postnatal day 91. The control groups received pure water or 2% sucrose for the control of hyperosmolarity. The effect on kidney weights, cystic indices, renal function, cell proliferation, and autophagic activities was determined. We found that Pkd1 miR Tg mice had a significantly lower renal mRNA expression of autophagy-related genes, including atg5, atg12, ulk1, beclin1, and p62, compared with wild-type control mice. Furthermore, immunohistochemical analysis showed that cystic lining cells had strong positive staining for the p62 protein, indicating impaired degradation of the protein by the autophagy-lysosome pathway. However, trehalose treatment did not improve reduced autophagy activities, nor did it reduce relative kidney weights, plasma blood urea nitrogen levels, or cystatin C levels in Pkd1 miR Tg mice. Histomorphological analysis revealed no significant differences in the renal cyst index, fibrosis score, or proliferative score among trehalose-, sucrose-, and water-treated groups. Our results demonstrate that adding trehalose to drinking water does not modulate autophagy activities and renal cystogenesis in Pkd1-deficient mice, suggesting that an oral supplement of trehalose may not affect the progression of ADPKD. MDPI 2018-12-25 /pmc/articles/PMC6356442/ /pubmed/30585217 http://dx.doi.org/10.3390/nu11010042 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chou, Li-Fang
Cheng, Ya-Lien
Hsieh, Chun-Yih
Lin, Chan-Yu
Yang, Huang-Yu
Chen, Yung-Chang
Hung, Cheng-Chieh
Tian, Ya-Chung
Yang, Chih-Wei
Chang, Ming-Yang
Effect of Trehalose Supplementation on Autophagy and Cystogenesis in a Mouse Model of Polycystic Kidney Disease
title Effect of Trehalose Supplementation on Autophagy and Cystogenesis in a Mouse Model of Polycystic Kidney Disease
title_full Effect of Trehalose Supplementation on Autophagy and Cystogenesis in a Mouse Model of Polycystic Kidney Disease
title_fullStr Effect of Trehalose Supplementation on Autophagy and Cystogenesis in a Mouse Model of Polycystic Kidney Disease
title_full_unstemmed Effect of Trehalose Supplementation on Autophagy and Cystogenesis in a Mouse Model of Polycystic Kidney Disease
title_short Effect of Trehalose Supplementation on Autophagy and Cystogenesis in a Mouse Model of Polycystic Kidney Disease
title_sort effect of trehalose supplementation on autophagy and cystogenesis in a mouse model of polycystic kidney disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356442/
https://www.ncbi.nlm.nih.gov/pubmed/30585217
http://dx.doi.org/10.3390/nu11010042
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