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Biochim Biophys Acta Mol Basis Dis. 2017 Jun;1863(6):1231-1241. doi: 10.1016/j.bbadis.2017.03.012. Epub 2017 Mar 23.

Aquaporin-3 deletion in mice results in renal collecting duct abnormalities and worsens ischemia-reperfusion injury.

Author information

1
Department of Pharmacology, School of Basic Medical Sciences, Peking University, State Key Laboratory of Natural and Biomimetic Drugs, and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing 100191, China.
2
Departments of Medicine and Physiology, University of California San Francisco, CA 94143, USA.
3
Department of Pharmacology, School of Basic Medical Sciences, Peking University, State Key Laboratory of Natural and Biomimetic Drugs, and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing 100191, China. Electronic address: baoxue@bjmu.edu.cn.

Abstract

Aquaporin-3 (AQP3), a transporter of water, glycerol and H2O2, is expressed in basolateral membranes of principal cells in kidney collecting duct. Here, we report that AQP3 deletion in mice affects renal function and modulates renal injury. We found collecting duct hyperplasia and cell swelling in kidneys of adult AQP3 null mice. After mild renal ischemia-reperfusion (IR), AQP3 null mice had significantly greater blood urea nitrogen (57mg/dl) and creatinine (136μM) than wild-type mice (35mg/dl and 48μM, respectively), and showed renal morphological changes, including tubular dilatation, erythrocyte diapedesis and collecting duct incompletion. MPO, MDA and SOD following IR in AQP3 null mice were significantly different from that in wild-type mice (1.7U/g vs 0.8U/g, 3.9μM/g vs 2.4μM/g, 6.4U/mg vs 11U/mg, respectively). Following IR, AQP3 deletion inhibited activation of mitogen-activated protein kinase (MAPK) signaling and produced an increase in the ratios of Bax/Bcl-2, cleaved caspase-3/caspase-3 and p-p53/p53. Studies in transfected MDCK cells showed that AQP3 expression attenuated reduced cell viability following hypoxia-reoxygenation, with reduced apoptosis and increased MAPK signaling. Our results support a novel role for AQP3 in modulating renal injury and suggest the mechanisms involved in protection against hypoxic injury.

KEYWORDS:

AQP3; Acute kidney injury; Ischemic injury; Kidney; MAPK; MDCK

PMID:
28344130
DOI:
10.1016/j.bbadis.2017.03.012
[Indexed for MEDLINE]
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