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

Nutrients ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 42 ◽  
Author(s):  
Li-Fang Chou ◽  
Ya-Lien Cheng ◽  
Chun-Yih Hsieh ◽  
Chan-Yu Lin ◽  
Huang-Yu Yang ◽  
...  

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.

2018 ◽  
Vol 9 (1) ◽  
pp. 389-396 ◽  
Author(s):  
Yangyang Zhu ◽  
Tian Teng ◽  
Hu Wang ◽  
Hao Guo ◽  
Lei Du ◽  
...  

Autosomal dominant polycystic kidney disease (ADPKD) is a common monogenic disease characterized by massive enlargement of fluid-filled cysts in the kidney.


2014 ◽  
Vol 88 (3) ◽  
pp. 412-421 ◽  
Author(s):  
Chaowalit Yuajit ◽  
Chatchai Muanprasat ◽  
Anna-Rachel Gallagher ◽  
Sorin V. Fedeles ◽  
Suticha Kittayaruksakul ◽  
...  

2009 ◽  
Vol 132 (2) ◽  
pp. 199-210 ◽  
Author(s):  
Larissa Osten ◽  
Marion Kubitza ◽  
Anna Rachel Gallagher ◽  
Jürgen Kastner ◽  
Heike Olbrich ◽  
...  

2011 ◽  
Vol 108 (44) ◽  
pp. 18067-18072 ◽  
Author(s):  
E. E. Olsan ◽  
S. Mukherjee ◽  
B. Wulkersdorfer ◽  
J. M. Shillingford ◽  
A. J. Giovannone ◽  
...  

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