Hypertonicity regulates the aquaporin-2 promoter independently of arginine vasopressin

Kasono, Keizo; Saito, T.; Saitô, Takako; Tamemoto, Hiroyuki; Yanagidate, Chieko; Uchida, Shinichi; Kawakami, Masanobu; Sasaki, Sei; Ishikawa, San‐e

doi:10.1093/ndt/gfh677

Cited by 43 publications

(39 citation statements)

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“…This escape phenomenon has been shown to depend on both nitric oxide and prostaglandin production (26). There is evidence that tonicity may be a significant signal (16,19). However, chronic furosemide treatment, which will also wash out the medullary gradient, did not decrease AQP2 levels in vivo (25, 37).…”

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confidence: 99%

Dehydration-induced increase in aquaporin-2 protein abundance is blocked by nonsteroidal anti-inflammatory drugs

Baggaley

Nielsen

Marples

2010

American Journal of Physiology-Renal Physiology

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It is now well established that the antidiuretic response to vasopressin is modulated by changes in aquaporin-2 (AQP2) expression in response to hydration status. While vasopressin itself is one signal driving expression, other signals also play a part. In this study, we planned to investigate whether prostaglandins, known to modulate AQP2 trafficking, may play a role in this process. Male Wistar rats were kept in metabolic cages, with either free access to water and food, or were given 15 g of food gelled with water, such that they were fluid restricted or fluid loaded. The effects of oral administration of two structurally different NSAIDs, indomethacin and ibuprofen, and a COX-2-selective NSAID, meloxicam, on urine output and AQP2 expression were investigated in kidneys removed under terminal anesthesia. All the NSAIDs decreased AQP2 expression significantly in water-restricted rats but did not significantly alter PGE excretion. In water-loaded rats, the effects were less marked, and meloxicam had no significant effect. Consistent with this, ibuprofen prevented the increase in AQP2 expression seen in response to dehydration. These results demonstrate that NSAIDs decrease AQP2 protein abundance, particularly during adaptation during dehydration. This may be of particular significance in older and critically ill patients, who are prone to dehydration.antidiuresis; vasopressin; collecting duct IT IS NOW WELL ESTABLISHED that the acute antidiuretic action of vasopressin depends on the exocytic insertion of aquaporin-2 (AQP2) water channels from a store in intracellular vesicles to the apical plasma membrane of collecting duct principal cells (13,24,29,34), the so-called "shuttle" mechanism. Furthermore, there is now clear evidence that this acute response is modulated by changes in the total amount of AQP2 present in the cells. Such changes occur in response to chronic alterations in hydration, with water loading causing a decrease in AQP2 expression, while dehydration increases the AQP2 levels (28). Changes in AQP2 expression are also found in association with a variety of pathological conditions associated with either excess water loss (1,7,11,12,23,25) or water retention (2,30,31,39).The signals associated with changes in AQP2 expression are currently being sought. One signal is vasopressin, which causes an increase in AQP2 expression when given as a chronic infusion to either Brattleboro rats (which lack endogenous vasopressin) (5) or normal rats (8,9). This effect is thought to be mediated by cAMP and protein kinase A, which also plays a pivotal role in the acute shuttling response, via phosphorylation of a CRE-binding protein, which then binds to the promoter of the AQP2 gene (38). However, it is now clear that vasopressin-independent pathways also play a role, since decreases in AQP2 are seen in association with the ability to lose water in the urine despite ongoing vasopressin infusion (vasopressin escape phenomenon) (8, 9). This escape phenomenon has been shown to depend on both nitric oxide and prostagl...

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confidence: 99%

Dehydration-induced increase in aquaporin-2 protein abundance is blocked by nonsteroidal anti-inflammatory drugs

Baggaley

Nielsen

Marples

2010

American Journal of Physiology-Renal Physiology

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“…Mutations in components of this pathway, especially in AVPR2 and AQP2, cause defects in urine concentration manifested as nephrogenic diabetes insipidus (NDI) (23). While AVP/AVPR2 signaling can regulate the long-term expression of AQP2 (35), regulation of AQP2 by AVP-independent mechanisms has also been reported (14,20,42).Although the hypertonic environment within the kidney allows for reabsorption of water, it also subjects cells to a potentially lethal osmotic stress. The cellular response that permits cells of the renal medulla to adapt and survive within a hypertonic environment is mediated by the tonicity-responsive enhancer binding protein (TonEBP)/nuclear factor of activated T cells (NFAT)5 transcription factor (13).…”

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confidence: 99%

Calcineurin-NFATc signaling pathway regulates AQP2 expression in response to calcium signals and osmotic stress

Li¹,

McDill²,

Kovach³

et al. 2007

American Journal of Physiology-Cell Physiology

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December 13, 2006; doi:10.1152/ajpcell.00588.2005.-The aquaporin (AQP)2 channel mediates the reabsorption of water in renal collecting ducts in response to arginine vasopressin (AVP) and hypertonicity. Here we show that AQP2 expression is induced not only by the tonicityresponsive enhancer binding protein (TonEBP)/nuclear factor of activated T cells (NFAT)5-mediated hypertonic stress response but also by the calcium-dependent calcineurin-NFATc pathway. The induction of AQP2 expression by the calcineurin-NFATc pathway can occur in the absence of TonEBP/NFAT5. Mutational and chromatin immunoprecipitation analyses revealed the existence of functional NFAT binding sites within the proximal AQP2 promoter responsible for regulation of AQP2 by NFATc proteins and TonEBP/NFAT5. Contrary to the notion that TonEBP/NFAT5 is the only Rel/NFAT family member regulated by tonicity, we found that hypertonicity promotes the nuclear translocation of NFATc proteins for the subsequent induction of AQP2 expression. Calcineurin activity was also found to be involved in the induction of TonEBP/NFAT5 expression by hypertonicity, thus further defining the signaling mechanisms that underlie the TonEBP/NFAT5 osmotic stress response pathway. The coordinate regulation of AQP2 expression by both osmotic stress and calcium signaling appears to provide a means to integrate diverse extracellular signals into optimal cellular responses. aquaporin; nuclear factor of activated T cells; tonicity-responsive enhancer binding protein; osmotic response CELLS OF THE RENAL MEDULLA exist in a unique tissue environment characterized by extremes of hypertonicity during periods of antidiuresis, which allows for the efficient reabsorption of water from the glomerular filtrate (3). The hypertonic interstitial environment allows water to diffuse through the tubular epithelial cell membrane via aquaporin (AQP) water channels. Genetic studies in both mice and humans indicate that multiple AQPs, including AQP2, play a critical role in water transport in the kidney (21). AQP2 is expressed in cells of the renal collecting ducts that are exposed to the potentially hypertonic environment. Binding of arginine vasopressin (AVP) to AVP receptor 2 (AVPR2) induces the translocation of AQP2 from storage vesicles to the plasma membrane (21). Mutations in components of this pathway, especially in AVPR2 and AQP2, cause defects in urine concentration manifested as nephrogenic diabetes insipidus (NDI) (23). While AVP/AVPR2 signaling can regulate the long-term expression of AQP2 (35), regulation of AQP2 by AVP-independent mechanisms has also been reported (14,20,42).Although the hypertonic environment within the kidney allows for reabsorption of water, it also subjects cells to a potentially lethal osmotic stress. The cellular response that permits cells of the renal medulla to adapt and survive within a hypertonic environment is mediated by the tonicity-responsive enhancer binding protein (TonEBP)/nuclear factor of activated T cells (NFAT)5 transcription factor (13). TonEBP/ NF...

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“…dDAVP Dependence of Tonicity-induced AQP2 Transcription-Tonicity can change AQP2 abundance independent of AVP in vivo (7,9). To test whether an AVP-independent effect of tonicity on AQP2 expression is also observed in our cells, mpkCCD-AQP2-3.0-luc cells were again treated with dif-FIGURE 2.…”

Section: Mpkccd Cells As a Model For Tonicity-induced Aqp2mentioning

confidence: 99%

“…In a rat animal model, it has been shown that the onset of this escape coincides with a decrease in the AQP2 expression in the renal collecting duct (6). Hypotonicity and/or volume expansion have been proposed to mediate this AVP-independent direct regulation of AQP2 expression (7).…”

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confidence: 99%

“…However, the role of TonEBP and its TonE element in AQP2 expression regulation is still controversial. In Madin Darby Canine Kidney (MDCK) cells, for example, Kasono et al observed a hypertonicity-induced increase in AQP2 transcription only when the AQP2 promoter was Ϫ6.1 kb or longer and therefore did not involve TonE, which localizes at 489 bases upstream of the AQP2 transcription start site (7). Moreover, the severe atrophy of the renal medulla in the TonEBP Ϫ/Ϫ and dominantnegative TonEBP-overexpressing mice complicates the interpretation of its direct involvement in AQP2 regulation.…”

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confidence: 99%

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Hypotonicity-induced Reduction of Aquaporin-2 Transcription in mpkCCD Cells Is Independent of the Tonicity Responsive Element, Vasopressin, and cAMP

Kortenoeven¹,

Brand²,

Wetzels

et al. 2011

Journal of Biological Chemistry

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The syndrome of inappropriate antidiuretic hormone secretion is characterized by excessive water uptake and hyponatremia. The extent of hyponatremia, however, is less than anticipated, which is ascribed to a defense mechanism, the vasopressin-escape, and is suggested to involve a tonicity-determined down-regulation of the water channel aquaporin-2 (AQP2). The underlying mechanism, however, is poorly understood. To study this, we used the mouse cortical collecting duct (mpkCCD) cell line. MpkCCD cells, transfected with an AQP2-promoter luciferase construct showed a reduced and increased AQP2 abundance and transcription following culture in hypotonic and hypertonic medium, respectively. This depended on tonicity rather than osmolality and occurred independently of the vasopressin analog dDAVP, cAMP levels, or protein kinase A activity. Although prostaglandins and nitric oxide reduced AQP2 abundance, inhibition of their synthesis did not influence tonicity-induced AQP2 transcription. Also, cells in which the cAMP or tonicity-responsive element (CRE/TonE) in the AQP2-promoter were mutated showed a similar response to hypotonicity. Instead, the tonicity-responsive elements were pin-pointed to nucleotides ؊283 to ؊252 and ؊157 to ؊126 bp. In conclusion, our data indicate that hypotonicity reduces AQP2 abundance and transcription, which occurs independently of vasopressin, cAMP, and the known TonE and CRE in the AQP2-promoter. Increased prostaglandin and nitric oxide, as found in vivo, may contribute to reduced AQP2 in vasopressin-escape, but do not mediate the effect of hypotonicity on AQP2 transcription. Our data suggest that two novel segments (؊283 to ؊252 and ؊157 to ؊126 bp) in the AQP2-promoter mediate the hypotonicity-induced AQP2 downregulation during vasopressin-escape.Renal water reabsorption is regulated by the hormone arginine vasopressin (AVP).2 AVP binding to its V2 receptor in renal principal cells induces a cAMP cascade leading to increased translocation of the water channel aquaporin-2 (AQP2) to the apical membrane, resulting in water reabsorption from the pro-urine (1). In addition to this short-term effect, cAMP increases AQP2 transcription through phosphorylation of the transcription factor CREB (cAMP responsive element-binding protein), which then binds to a cAMP responsive element (CRE) at Ϫ210 in the AQP2 promoter (2, 3). The increase in transcription is a more long-term effect, requiring hours to take effect. AVP synthesis and release are regulated by alterations in plasma osmolality as well as non-osmotic, baroreceptor-mediated pathways (4). Osmolality not only affects plasma AVP, but also appears to have direct effects on urine concentrating ability and AQP2 expression. In the syndrome of inappropriate antidiuretic hormone secretion (SIADH), for example, levels of AVP are inappropriately high relative to plasma osmolality, resulting in free-water retention and hypotonicity. Under these circumstances, however, the free-water excretion is considerably higher than would be expected from the vaso...

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Hypertonicity regulates the aquaporin-2 promoter independently of arginine vasopressin

Cited by 43 publications

References 17 publications

Dehydration-induced increase in aquaporin-2 protein abundance is blocked by nonsteroidal anti-inflammatory drugs

Dehydration-induced increase in aquaporin-2 protein abundance is blocked by nonsteroidal anti-inflammatory drugs

Calcineurin-NFATc signaling pathway regulates AQP2 expression in response to calcium signals and osmotic stress

Hypotonicity-induced Reduction of Aquaporin-2 Transcription in mpkCCD Cells Is Independent of the Tonicity Responsive Element, Vasopressin, and cAMP

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