New insights into the transcriptional regulation of aquaporin-2 and the treatment of X-linked hereditary nephrogenic diabetes insipidus

Abstract

The kidney regulates the balance of water, electrolytes, and acids and bases (pH) in the body. Two critical components for urine concentration in the kidney are: 1) an interstitial osmolality, which provides a driving force for tubular water reabsorption; and 2) the osmotic water permeability of the tubular epithelia, which depends on expression of aquaporin (AQP) water-channel proteins in the cell membrane [1,2]. Consistent with these components, conditions that result in defective urine concentration, such as lithium treatment, are associated with decreased medullary organic osmolytes (e.g., betaine, myo-inositol, taurine, and glycerophosphocholine) [3]. Because of high osmotic permeability of water in the tubular epithelia, proximal tubules and descending thin limbs allow the reabsorption of a majority of the water filtered in the glomerulus, where aquaporin-1 (AQP1) mediates near-isosmotic fluid reabsorption [4-6]. AQP1 is also expressed in the descending thin limb and descending vasa recta and facilitates countercurrent exchange in

Phosphoproteomic Identification of Vasopressin/cAMP/Protein Kinase A–Dependent Signaling in Kidney

“…The most thoroughly studied of these processes are the actions of vasopressin to increase Aqp2 gene transcription (Hasler et al, 2002;Sandoval et al, 2016) and the action of vasopressin to regulate membrane trafficking of the AQP2 protein to increase its abundance in the plasma membrane of collecting duct cells (Nielsen et al, 1995). Detailed discussion of the cellular level responses in Table 1 is beyond the scope of this treatise, but can be found in prior review articles (Knepper, 1997;Knepper and Inoue, 1997;Sasaki et al, 1998;Brown et al, 1998;Verkman, 1999;Nielsen et al, 1999Nielsen et al, , 2002Klussmann and Rosenthal, 2001;Brown, 2003;Valenti et al, 2005;Noda and Sasaki, 2005;Bichet, 2006;Boone and Deen, 2008;Moeller and Fenton, 2012;Fenton et al, 2013;Jung and Kwon, 2016;Jung and Kwon, 2019). One goal of this review is to map recently obtained phosphoproteomic data from both native and cultured collecting duct cells to the processes summarized in Table 1 in order to identify the signaling events responsible for the physiological responses.…”

Vasopressin-Independent Regulation of Aquaporin-2 by Tamoxifen in Kidney Collecting Ducts

“…This initiates a cascade leading to an increase in cAMP levels and activation of protein kinase A (PKA)-dependent phosphorylation of AQP2 at the serine 256 residue (pS256-AQP2). This is the main pathway of AQP2 trafficking to the apical plasma membrane of the collecting duct principal cells, which increases the osmotic water permeability (Katsura et al, 1997; Kortenoeven and Fenton, 2014; Jung and Kwon, 2016, 2019). However, several other factors/hormones contributing to AQP2 regulation have also been demonstrated over the recent years, thus increasing complexity (Chou et al, 2000; Fenton et al, 2013; Cheema et al, 2015; Milano et al, 2017; Ando and Uchida, 2018; Tingskov et al, 2018; Ranieri et al, 2019).…”

“…However, several other factors/hormones contributing to AQP2 regulation have also been demonstrated over the recent years, thus increasing complexity (Chou et al, 2000; Fenton et al, 2013; Cheema et al, 2015; Milano et al, 2017; Ando and Uchida, 2018; Tingskov et al, 2018; Ranieri et al, 2019). Although cAMP/PKA signaling is a critical regulatory pathway in the AVP-mediated AQP2 expression and trafficking, it has been discovered that modulation of calmodulin, Wnt5, prostaglandin E2, and cGMP pathways also influences AQP2 regulation and trafficking (Bouley et al, 2005; Hoffert et al, 2005; Olesen et al, 2011; Jung and Kwon, 2016, 2019).…”

Hyponatremia Associated with Pulmonary Arterial Hypertension: Syndrome of Inappropriate Antidiuresis Versus Right Heart Failure

“…Can NSIAD be induced by pulmonary disorders? The lung may be an important endocrine organ in disease 19) , and a certain signaling cascade may reach the kidney and act as a ligand to the vasopressin-2 receptor, thereby stimulating aquaporin-2 trafficking and production 20) . Further studies are required to elucidate the mechanisms by which various pulmonary disorders cause SIAD.…”