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

被引:15
作者
Chou, Li-Fang [1 ]
Cheng, Ya-Lien [1 ]
Hsieh, Chun-Yih [1 ]
Lin, Chan-Yu [1 ]
Yang, Huang-Yu [1 ]
Chen, Yung-Chang [1 ]
Hung, Cheng-Chieh [1 ]
Tian, Ya-Chung [1 ]
Yang, Chih-Wei [1 ]
Chang, Ming-Yang [1 ]
机构
[1] Chang Gung Univ, Chang Gung Mem Hosp, Dept Nephrol, Kidney Res Ctr,Coll Med, Taoyuan, Taiwan
关键词
autophagy; polycystic kidney disease; trehalose; MTOR; PROGRESSION; NEURODEGENERATION; ACTIVATION; PATHOLOGY; INSIGHTS; HYPOXIA; MICE;
D O I
10.3390/nu11010042
中图分类号
R15 [营养卫生、食品卫生]; TS201 [基础科学];
学科分类号
100403 ;
摘要
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.
引用
收藏
页数:16
相关论文
共 52 条
[1]   Multidrug Therapy for Polycystic Kidney Disease: A Review and Perspective [J].
Aguiari, Gianluca ;
Catizone, Luigi ;
del Senno, Laura .
AMERICAN JOURNAL OF NEPHROLOGY, 2013, 37 (02) :175-182
[2]   Unfolding osmotic demyelination [J].
Aguilar, Andrea .
NATURE REVIEWS NEPHROLOGY, 2017, 13 (04) :192-192
[3]   Hypoxia-inducible factor-1α (HIF-1α) and autophagy in polycystic kidney disease (PKD) [J].
Belibi, Franck ;
Zafar, Iram ;
Ravichandran, Kameswaran ;
Segvic, Anamarija Bauer ;
Jani, Alkesh ;
Ljubanovic, Danica Galesic ;
Edelstein, Charles L. .
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2011, 300 (05) :F1235-F1243
[4]   MONITORING AUTOPHAGIC DEGRADATION OF P62/SQSTM1 [J].
Bjorkoy, Geir ;
Lamark, Trond ;
Pankiv, Serhiy ;
Overvatn, Aud ;
Brech, Andreas ;
Johansen, Terje .
METHODS IN ENZYMOLOGY: AUTOPHAGY IN MAMMALIAN SYSTEMS, VOL 452, PT B, 2009, 452 :181-197
[5]   Endothelin B receptor blockade accelerates disease progression in a murine model of autosomal dominant polycystic kidney disease [J].
Chang, Ming-Yang ;
Parker, Emma ;
El Nahas, Meguid ;
Haylor, John L. ;
Ong, Albert C. M. .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2007, 18 (02) :560-569
[6]   Effect of celastrol on the progression of polycystic kidney disease in a Pkd1-deficient mouse model [J].
Chang, Ming-Yang ;
Hsieh, Chun-Yih ;
Lin, Chan-Yu ;
Chen, Di ;
Yang, Huang-Yu ;
Chen, Kuan-Hsing ;
Hsu, Hsiang-Hao ;
Tian, Ya-Chung ;
Chen, Yung-Chang ;
Hung, Cheng-Chieh ;
Yang, Chih-Wei .
LIFE SCIENCES, 2018, 212 :70-79
[7]   Targeting new cellular disease pathways in autosomal dominant polycystic kidney disease [J].
Chang, Ming-Yang ;
Ong, Albert C. M. .
NEPHROLOGY DIALYSIS TRANSPLANTATION, 2018, 33 (08) :1310-1316
[8]   The cell biology of polycystic kidney disease [J].
Chapin, Hannah C. ;
Caplan, Michael J. .
JOURNAL OF CELL BIOLOGY, 2010, 191 (04) :701-710
[9]   Role of trehalose phosphate synthase and trehalose during hypoxia: from flies to mammals [J].
Chen, QF ;
Haddad, GG .
JOURNAL OF EXPERIMENTAL BIOLOGY, 2004, 207 (18) :3125-3129
[10]   2-Deoxy-D-Glucose Ameliorates PKD Progression [J].
Chiaravalli, Marco ;
Rowe, Isaline ;
Mannella, Valeria ;
Quilici, Giacomo ;
Canu, Tamara ;
Bianchi, Veronica ;
Gurgone, Antonia ;
Antunes, Sofia ;
D'Adamo, Patrizia ;
Esposito, Antonio ;
Musco, Giovanna ;
Boletta, Alessandra .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2016, 27 (07) :1958-1969