Effect of Trehalose Supplementation on Autophagy and Cystogenesis in a Mouse Model of Polycystic Kidney Disease
| Autor: | Ya-Chung Tian, Cheng-Chieh Hung, Chun-Yih Hsieh, Huang-Yu Yang, Ya-Lien Cheng, Li-Fang Chou, Yung-Chang Chen, Ming-Yang Chang, Chan-Yu Lin, Chih-Wei Yang |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Blood Glucose medicine.medical_specialty autophagy ATG5 Autosomal dominant polycystic kidney disease lcsh:TX341-641 Mice Transgenic urologic and male genital diseases Kidney Article ATG12 03 medical and health sciences chemistry.chemical_compound Mice Internal medicine medicine Polycystic kidney disease Animals Genetic Predisposition to Disease Nutrition and Dietetics polycystic kidney disease biology Autophagy Trehalose medicine.disease Polycystic Kidney Autosomal Dominant MicroRNAs 030104 developmental biology Endocrinology medicine.anatomical_structure chemistry Cystatin C biology.protein lcsh:Nutrition. Foods and food supply Food Science |
| Zdroj: | Nutrients Volume 11 Issue 1 Nutrients, Vol 11, Iss 1, p 42 (2018) |
| ISSN: | 2072-6643 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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