Enhanced Autophagy in Polycystic Kidneys of AQP11 Null Mice
by
Yasuko Tanaka 1,*, Mayumi Watari 1, Tatsuya Saito 1, Yoshiyuki Morishita 2 and Kenichi Ishibashi 1
Yasuko Tanaka 1,*, Mayumi Watari 1, Tatsuya Saito 1, Yoshiyuki Morishita 2 and Kenichi Ishibashi 1
1
Department of Pathophysiology, Faculty of Pharmacy, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan
2
Department of Nephrology, Saitama Medical Center, Jichi Medical University, 1-847 Ohmiya, Saitama-City, Saitama 330-8503, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: Gregor Drummen
Int. J. Mol. Sci. 2016, 17(12), 1993; https://doi.org/10.3390/ijms17121993
Received: 28 May 2016 / Revised: 14 November 2016 / Accepted: 16 November 2016 / Published: 30 November 2016
(This article belongs to the Special Issue Aquaporin)
Aquaporin-11 (AQP11) is an intracellular water channel expressed at the endoplasmic reticulum (ER) of the proximal tubule. Its gene disruption in mice leads to intracellular vacuole formation at one week and the subsequent development of polycystic kidneys by three weeks. As the damaged proximal tubular cells with intracellular vacuoles form cysts later, we postulated that autophagy may play a role in the cyst formation and examined autophagy activity before and after cyst development in AQP11(−/−) kidneys. PCR analysis showed the increased expression of the transcript encoding LC3 (Map1lc3b) as well as other autophagy-related genes in AQP11(−/−) mice. Using green fluorescent protein (GFP)-LC3 transgenic mice and AQP11(−/−) mice, we found that the number of GFP-LC3–positive puncta was increased in the proximal tubule of AQP11(−/−) mice before the cyst formation. Interestingly, they were also observed in the cyst-lining epithelial cell. Further PCR analyses revealed the enhanced expression of apoptosis-related and ER stress–related caspase genes before and after the cyst formation, which may cause the enhanced autophagy. These results suggest the involvement of autophagy in the development and maintenance of kidney cysts in AQP11(−/−) mice.
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Keywords:
proximal tubule; LC3; ER stress; apoptosis; PKD
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Tanaka, Y.; Watari, M.; Saito, T.; Morishita, Y.; Ishibashi, K. Enhanced Autophagy in Polycystic Kidneys of AQP11 Null Mice. Int. J. Mol. Sci. 2016, 17, 1993.
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