These authors contributed equally to this work.
Aquaporin-2 regulation in health and disease
Version of Record online: 6 NOV 2012
© 2012 American Society for Veterinary Clinical Pathology
Veterinary Clinical Pathology
Volume 41, Issue 4, pages 455–470, December 2012
How to Cite
Judith Radin, M., Yu, M.-J., Stoedkilde, L., Lance Miller, R., Hoffert, J. D., Frokiaer, J., Pisitkun, T. and Knepper, M. A. (2012), Aquaporin-2 regulation in health and disease. Veterinary Clinical Pathology, 41: 455–470. doi: 10.1111/j.1939-165x.2012.00488.x
- Issue online: 14 DEC 2012
- Version of Record online: 6 NOV 2012
- syndrome of inappropriate antidiuretic hormone excess;
Aquaporin-2 (AQP2), the vasopressin-regulated water channel of the renal collecting duct, is dysregulated in numerous disorders of water balance in people and animals, including those associated with polyuria (urinary tract obstruction, hypokalemia, inflammation, and lithium toxicity) and with dilutional hyponatremia (syndrome of inappropriate antidiuresis, congestive heart failure, cirrhosis). Normal regulation of AQP2 by vasopressin involves 2 independent regulatory mechanisms: (1) short-term regulation of AQP2 trafficking to and from the apical plasma membrane, and (2) long-term regulation of the total abundance of the AQP2 protein in the cells. Most disorders of water balance are the result of dysregulation of processes that regulate the total abundance of AQP2 in collecting duct cells. In general, the level of AQP2 in a collecting duct cell is determined by a balance between production via translation of AQP2 mRNA and removal via degradation or secretion into the urine in exosomes. AQP2 abundance increases in response to vasopressin chiefly due to increased translation subsequent to increases in AQP2 mRNA. Vasopressin-mediated regulation of AQP2 gene transcription is poorly understood, although several transcription factor-binding elements in the 5′ flanking region of the AQP2 gene have been identified, and candidate transcription factors corresponding to these elements have been discovered in proteomics studies. Here, we review progress in this area and discuss elements of vasopressin signaling in the collecting duct that may impinge on regulation of AQP2 in health and in the context of examples of polyuric diseases.