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  • Review Article
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Aquaporins in kidney pathophysiology

Abstract

Seven aquaporin water channels are expressed in human kidneys, and they have key roles in maintaining body water homeostasis. Impairment of their function can result in nephrogenic diabetes insipidus and other water-balance disorders. A lot of data have increased understanding of the functions and mechanisms of regulation of aquaporins both at the molecular and the clinical level. Research has also focused on aquaporins as therapeutic targets. This Review describes recent progress in uncovering the physiology and pathophysiology of aquaporins in the kidney, with particular attention devoted to AQP2, the most well-studied member of this protein group.

Key Points

  • Aquaporins are a family of membrane proteins that function as water-permeable channels

  • Seven different aquaporins are known to be expressed in the human kidney: AQP1, AQP2, AQP3, AQP4, AQP6, AQP7 and AQP11

  • AQP2, for which the most data are available, is vasopressin-sensitive and is expressed in the principal cells of the collecting duct; its impairment results in nephrogenic diabetes insipidus and other water balance disorders

  • Genetic defects in aquaporins other than AQP2 expressed in the kidney seem very rare and are associated with either mild defects (as for AQP1 and AQP7) or with no obvious deleterious consequence

  • AQP3 and AQP4 are expressed in the basolateral membrane of the principal cells of the collecting duct and represent potential exit pathways from these cells for water entering via AQP2

  • Besides being water-permeable, AQP6 and AQP7 are also permeable to anions and glycerol, respectively, so that AQP6 is suggested to be involved in acid secretion and AQP7 in glycerol metabolism

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Figure 1: Structure of aquaporin-2 embedded in the cell membrane reporting the protein mutations that cause nephrogenic diabetes insipidus.
Figure 2: Mechanism of AQP2 translocation from the cytoplasm of principal cells of the collecting duct to the membrane.

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Acknowledgements

Our research work is supported in part by Grant-in-Aid for Creative Scientific Research from the Japan Society for the Promotion of Science (17GS0312).

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Noda, Y., Sohara, E., Ohta, E. et al. Aquaporins in kidney pathophysiology. Nat Rev Nephrol 6, 168–178 (2010). https://doi.org/10.1038/nrneph.2009.231

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