Jørgen Frøkiær

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

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Vasopressin-Independent Regulation of Aquaporin-2 by Tamoxifen in Kidney Collecting Ducts. / Tingskov, Stine Julie; Choi, Hyo-Jung; Holst, Mikkel R.; Hu, Shan; Li, Chunling; Wang, Weidong; Frokiaer, Jorgen; Nejsum, Lene N.; Kwon, Tae-Hwan; Norregaard, Rikke.

In: Frontiers in Physiology, Vol. 10, 948, 08.2019, p. 1-13.

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Tingskov, Stine Julie ; Choi, Hyo-Jung ; Holst, Mikkel R. ; Hu, Shan ; Li, Chunling ; Wang, Weidong ; Frokiaer, Jorgen ; Nejsum, Lene N. ; Kwon, Tae-Hwan ; Norregaard, Rikke. / Vasopressin-Independent Regulation of Aquaporin-2 by Tamoxifen in Kidney Collecting Ducts. In: Frontiers in Physiology. 2019 ; Vol. 10. pp. 1-13.

Bibtex

@article{acc3038aa31b4270a1c4eaba4ec81eda,
title = "Vasopressin-Independent Regulation of Aquaporin-2 by Tamoxifen in Kidney Collecting Ducts",
abstract = "Arginine vasopressin (AVP) mediates water reabsorption in the kidney collecting ducts through regulation of aquaporin-2 (AQP2). Also, estrogen has been known to regulate AQP2. Consistently, we previously demonstrated that tamoxifen (TAM), a selective estrogen receptor modulator, attenuates the downregulation of AQP2 in lithium-induced nephrogenic diabetes insipidus (NDI). In this study, we investigated the AVP-independent regulation of AQP2 by TAM and the therapeutic effect of TAM on the dysregulation of AQP2 and impaired urinary concentration in a unilateral ureteral obstruction (UUO) model. Primary cultured inner medullary collecting duct (IMCD) cells from kidneys of male Sprague-Dawley rats were treated with TAM. Rats subjected to 7 days of UUO were treated with TAM by oral gavage. Changes of intracellular trafficking and expression of AQP2 were evaluated by quantitative PCR, Western blotting, and immunohistochemistry. TAM induced AQP2 protein expression and intracellular trafficking in primary cultured IMCD cells, which were independent of the vasopressin V2 receptor (V2R) and cAMP activation, the critical pathways involved in AVP-stimulated regulation of AQP2. TAM attenuated the downregulation of AQP2 in TGF-beta treated IMCD cells and IMCD suspensions prepared from UUO rats. TAM administration in vivo attenuated the downregulation of AQP2, associated with an improvement of urinary concentration in UUO rats. In addition, TAM increased CaMKII expression, suggesting that calmodulin signaling pathway is likely to be involved in the TAM-mediated AQP2 regulation. In conclusion, TAM is involved in AQP2 regulation in a vasopressin-independent manner and improves urinary concentration by attenuating the downregulation of AQP2 and maintaining intracellular trafficking in UUO.",
keywords = "Aquaporin-2, inner medullary collecting duct, tamoxifen, unilateral ureteral obstruction, vasopressin, ESTROGEN-RECEPTOR-ALPHA, DOWN-REGULATION, RENAL AQUAPORINS, AQP2 EXPRESSION, KINASE-II, PROTEIN, WATER, TRAFFICKING, GENE, PHOSPHORYLATION",
author = "Tingskov, {Stine Julie} and Hyo-Jung Choi and Holst, {Mikkel R.} and Shan Hu and Chunling Li and Weidong Wang and Jorgen Frokiaer and Nejsum, {Lene N.} and Tae-Hwan Kwon and Rikke Norregaard",
year = "2019",
month = aug,
doi = "10.3389/fphys.2019.00948",
language = "English",
volume = "10",
pages = "1--13",
journal = "Frontiers in Physiology",
issn = "1664-042X",
publisher = "Frontiers Media S.A",

}

RIS

TY - JOUR

T1 - Vasopressin-Independent Regulation of Aquaporin-2 by Tamoxifen in Kidney Collecting Ducts

AU - Tingskov, Stine Julie

AU - Choi, Hyo-Jung

AU - Holst, Mikkel R.

AU - Hu, Shan

AU - Li, Chunling

AU - Wang, Weidong

AU - Frokiaer, Jorgen

AU - Nejsum, Lene N.

AU - Kwon, Tae-Hwan

AU - Norregaard, Rikke

PY - 2019/8

Y1 - 2019/8

N2 - Arginine vasopressin (AVP) mediates water reabsorption in the kidney collecting ducts through regulation of aquaporin-2 (AQP2). Also, estrogen has been known to regulate AQP2. Consistently, we previously demonstrated that tamoxifen (TAM), a selective estrogen receptor modulator, attenuates the downregulation of AQP2 in lithium-induced nephrogenic diabetes insipidus (NDI). In this study, we investigated the AVP-independent regulation of AQP2 by TAM and the therapeutic effect of TAM on the dysregulation of AQP2 and impaired urinary concentration in a unilateral ureteral obstruction (UUO) model. Primary cultured inner medullary collecting duct (IMCD) cells from kidneys of male Sprague-Dawley rats were treated with TAM. Rats subjected to 7 days of UUO were treated with TAM by oral gavage. Changes of intracellular trafficking and expression of AQP2 were evaluated by quantitative PCR, Western blotting, and immunohistochemistry. TAM induced AQP2 protein expression and intracellular trafficking in primary cultured IMCD cells, which were independent of the vasopressin V2 receptor (V2R) and cAMP activation, the critical pathways involved in AVP-stimulated regulation of AQP2. TAM attenuated the downregulation of AQP2 in TGF-beta treated IMCD cells and IMCD suspensions prepared from UUO rats. TAM administration in vivo attenuated the downregulation of AQP2, associated with an improvement of urinary concentration in UUO rats. In addition, TAM increased CaMKII expression, suggesting that calmodulin signaling pathway is likely to be involved in the TAM-mediated AQP2 regulation. In conclusion, TAM is involved in AQP2 regulation in a vasopressin-independent manner and improves urinary concentration by attenuating the downregulation of AQP2 and maintaining intracellular trafficking in UUO.

AB - Arginine vasopressin (AVP) mediates water reabsorption in the kidney collecting ducts through regulation of aquaporin-2 (AQP2). Also, estrogen has been known to regulate AQP2. Consistently, we previously demonstrated that tamoxifen (TAM), a selective estrogen receptor modulator, attenuates the downregulation of AQP2 in lithium-induced nephrogenic diabetes insipidus (NDI). In this study, we investigated the AVP-independent regulation of AQP2 by TAM and the therapeutic effect of TAM on the dysregulation of AQP2 and impaired urinary concentration in a unilateral ureteral obstruction (UUO) model. Primary cultured inner medullary collecting duct (IMCD) cells from kidneys of male Sprague-Dawley rats were treated with TAM. Rats subjected to 7 days of UUO were treated with TAM by oral gavage. Changes of intracellular trafficking and expression of AQP2 were evaluated by quantitative PCR, Western blotting, and immunohistochemistry. TAM induced AQP2 protein expression and intracellular trafficking in primary cultured IMCD cells, which were independent of the vasopressin V2 receptor (V2R) and cAMP activation, the critical pathways involved in AVP-stimulated regulation of AQP2. TAM attenuated the downregulation of AQP2 in TGF-beta treated IMCD cells and IMCD suspensions prepared from UUO rats. TAM administration in vivo attenuated the downregulation of AQP2, associated with an improvement of urinary concentration in UUO rats. In addition, TAM increased CaMKII expression, suggesting that calmodulin signaling pathway is likely to be involved in the TAM-mediated AQP2 regulation. In conclusion, TAM is involved in AQP2 regulation in a vasopressin-independent manner and improves urinary concentration by attenuating the downregulation of AQP2 and maintaining intracellular trafficking in UUO.

KW - Aquaporin-2

KW - inner medullary collecting duct

KW - tamoxifen

KW - unilateral ureteral obstruction

KW - vasopressin

KW - ESTROGEN-RECEPTOR-ALPHA

KW - DOWN-REGULATION

KW - RENAL AQUAPORINS

KW - AQP2 EXPRESSION

KW - KINASE-II

KW - PROTEIN

KW - WATER

KW - TRAFFICKING

KW - GENE

KW - PHOSPHORYLATION

U2 - 10.3389/fphys.2019.00948

DO - 10.3389/fphys.2019.00948

M3 - Journal article

C2 - 31447686

VL - 10

SP - 1

EP - 13

JO - Frontiers in Physiology

JF - Frontiers in Physiology

SN - 1664-042X

M1 - 948

ER -