Aquaporin-2 abundance in the renal collecting duct: new insights from cultured cell models.
The renal cortico-papillary osmotic gradient is generated by sodium reabsorption in the thick ascending limb. The antidiuretic hormone arginine vasopressin (AVP) increases collecting duct water permeability by enhancing aquaporin-2 (AQP2) water channel insertion in the apical membrane of principal cells, allowing water to passively flow along the osmotic gradient from the tubule lumen to the interstitium. In addition to short-term AQP2 redistribution between intracellular compartments and the cell surface, AQP2 whole cell abundance is tightly regulated. AVP is a major transcriptional activator of the AQP2 gene, and stimulation of insulin- and calcium-sensing receptors respectively potentiate and reduce its action. Extracellular tonicity is another key factor that determines the levels of AQP2 abundance. Its effect is dependent on activation of the tonicity-responsive enhancer binding protein that reinforces AVP-induced AQP2 transcriptional activation. Conversely, activation of the NF-kappaB transcriptional factor by proinflammatory factors reduces AQP2 gene transcription. Aldosterone additionally regulates AQP2 whole cell abundance by simultaneously reducing AQP2 gene transcription and stimulating AQP2 mRNA translation. These examples illustrate how cross talk between various stimuli regulates AQP2 abundance in collecting duct principal cells and consequently contributes to maintenance of body water homeostasis.
Hasler
Udo
U
Service de Néphrologie, Fondation pour Recherches Médicales, 1211 Geneva 4, Switzerland. eric.feraille@unige.ch
Leroy
Valérie
V
Martin
Pierre-Yves
PY
Féraille
Eric
E
D051399:Aquaporin 2 / Q000378:metabolism*; D001127:Arginine Vasopressin / Q000378:metabolism; D001834:Body Water / Q000378:metabolism; D002478:Cells, Cultured; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007685:Kidney Tubules, Collecting / Q000166:cytology* / Q000378:metabolism*; D008954:Models, Biological; D009995:Osmosis / Q000502:physiology
D051399:Aquaporin 2; D001127:Arginine Vasopressin