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

Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
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Nutrients 2019, 11(1), 42; https://doi.org/10.3390/nu11010042
Received: 29 November 2018 / Revised: 15 December 2018 / Accepted: 20 December 2018 / Published: 25 December 2018
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. View Full-Text
Keywords: autophagy; polycystic kidney disease; trehalose autophagy; polycystic kidney disease; trehalose
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MDPI and ACS Style

Chou, L.-F.; Cheng, Y.-L.; Hsieh, C.-Y.; Lin, C.-Y.; Yang, H.-Y.; Chen, Y.-C.; Hung, C.-C.; Tian, Y.-C.; Yang, C.-W.; Chang, M.-Y. Effect of Trehalose Supplementation on Autophagy and Cystogenesis in a Mouse Model of Polycystic Kidney Disease. Nutrients 2019, 11, 42. https://doi.org/10.3390/nu11010042

AMA Style

Chou L-F, Cheng Y-L, Hsieh C-Y, Lin C-Y, Yang H-Y, Chen Y-C, Hung C-C, Tian Y-C, Yang C-W, Chang M-Y. Effect of Trehalose Supplementation on Autophagy and Cystogenesis in a Mouse Model of Polycystic Kidney Disease. Nutrients. 2019; 11(1):42. https://doi.org/10.3390/nu11010042

Chicago/Turabian Style

Chou, Li-Fang, Ya-Lien Cheng, Chun-Yih Hsieh, Chan-Yu Lin, Huang-Yu Yang, Yung-Chang Chen, Cheng-Chieh Hung, Ya-Chung Tian, Chih-Wei Yang, and Ming-Yang Chang. 2019. "Effect of Trehalose Supplementation on Autophagy and Cystogenesis in a Mouse Model of Polycystic Kidney Disease" Nutrients 11, no. 1: 42. https://doi.org/10.3390/nu11010042

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