title: Enhanced Autophagy in Polycystic Kidneys of AQP11 Null Mice.
abstract: 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.
authors.affiliation: Department of Pathophysiology, Faculty of Pharmacy, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan. ystanaka@my-pharm.ac.jp.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Pathophysiology, Faculty of Pharmacy, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan. mayuwata1204@icloud.com.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Watari
authors.affiliation: Department of Pathophysiology, Faculty of Pharmacy, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan. tsaito@my-pharm.ac.jp.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department of Nephrology, Saitama Medical Center, Jichi Medical University, 1-847 Ohmiya, Saitama-City, Saitama 330-8503, Japan. ymori@jichi.ac.jp.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Morishita
authors.affiliation: Department of Pathophysiology, Faculty of Pharmacy, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan. kishiba@my-pharm.ac.jp.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ishibashi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D020346:Aquaporins / Q000172:deficiency* / Q000235:genetics; D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D015153:Blotting, Western; D059865:Endoplasmic Reticulum Stress / Q000235:genetics / Q000502:physiology; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D007690:Polycystic Kidney Diseases / Q000378:metabolism / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C503878:Aqp11 protein, mouse; D020346:Aquaporins
keywords: ER stress; LC3; PKD; apoptosis; proximal tubule