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

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 downr...
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Autor*in:	Stine Julie Tingskov [verfasserIn] Hyo-Jung Choi [verfasserIn] Mikkel R. Holst [verfasserIn] Shan Hu [verfasserIn] Chunling Li [verfasserIn] Weidong Wang [verfasserIn] Jørgen Frøkiær [verfasserIn] Lene N. Nejsum [verfasserIn] Tae-Hwan Kwon [verfasserIn] Rikke Nørregaard [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

Schlagwörter:	Aquaporin-2 inner medullary collecting duct tamoxifen unilateral ureteral obstruction vasopressin

Übergeordnetes Werk:	In: Frontiers in Physiology - Frontiers Media S.A., 2011, 10(2019)
Übergeordnetes Werk:	volume:10 ; year:2019

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fphys.2019.00948

Katalog-ID:	DOAJ033661197

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allfields	10.3389/fphys.2019.00948 doi (DE-627)DOAJ033661197 (DE-599)DOAJ41b4fc3c33514cb58d811ce65c2fe4cd DE-627 ger DE-627 rakwb eng QP1-981 Stine Julie Tingskov verfasserin aut Vasopressin-Independent Regulation of Aquaporin-2 by Tamoxifen in Kidney Collecting Ducts 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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-β 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. Aquaporin-2 inner medullary collecting duct tamoxifen unilateral ureteral obstruction vasopressin Physiology Hyo-Jung Choi verfasserin aut Mikkel R. Holst verfasserin aut Shan Hu verfasserin aut Chunling Li verfasserin aut Weidong Wang verfasserin aut Jørgen Frøkiær verfasserin aut Lene N. Nejsum verfasserin aut Tae-Hwan Kwon verfasserin aut Rikke Nørregaard verfasserin aut In Frontiers in Physiology Frontiers Media S.A., 2011 10(2019) (DE-627)631498788 (DE-600)2564217-0 1664042X nnns volume:10 year:2019 https://doi.org/10.3389/fphys.2019.00948 kostenfrei https://doaj.org/article/41b4fc3c33514cb58d811ce65c2fe4cd kostenfrei https://www.frontiersin.org/article/10.3389/fphys.2019.00948/full kostenfrei https://doaj.org/toc/1664-042X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2019
spelling	10.3389/fphys.2019.00948 doi (DE-627)DOAJ033661197 (DE-599)DOAJ41b4fc3c33514cb58d811ce65c2fe4cd DE-627 ger DE-627 rakwb eng QP1-981 Stine Julie Tingskov verfasserin aut Vasopressin-Independent Regulation of Aquaporin-2 by Tamoxifen in Kidney Collecting Ducts 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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-β 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. Aquaporin-2 inner medullary collecting duct tamoxifen unilateral ureteral obstruction vasopressin Physiology Hyo-Jung Choi verfasserin aut Mikkel R. Holst verfasserin aut Shan Hu verfasserin aut Chunling Li verfasserin aut Weidong Wang verfasserin aut Jørgen Frøkiær verfasserin aut Lene N. Nejsum verfasserin aut Tae-Hwan Kwon verfasserin aut Rikke Nørregaard verfasserin aut In Frontiers in Physiology Frontiers Media S.A., 2011 10(2019) (DE-627)631498788 (DE-600)2564217-0 1664042X nnns volume:10 year:2019 https://doi.org/10.3389/fphys.2019.00948 kostenfrei https://doaj.org/article/41b4fc3c33514cb58d811ce65c2fe4cd kostenfrei https://www.frontiersin.org/article/10.3389/fphys.2019.00948/full kostenfrei https://doaj.org/toc/1664-042X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2019
allfields_unstemmed	10.3389/fphys.2019.00948 doi (DE-627)DOAJ033661197 (DE-599)DOAJ41b4fc3c33514cb58d811ce65c2fe4cd DE-627 ger DE-627 rakwb eng QP1-981 Stine Julie Tingskov verfasserin aut Vasopressin-Independent Regulation of Aquaporin-2 by Tamoxifen in Kidney Collecting Ducts 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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-β 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. Aquaporin-2 inner medullary collecting duct tamoxifen unilateral ureteral obstruction vasopressin Physiology Hyo-Jung Choi verfasserin aut Mikkel R. Holst verfasserin aut Shan Hu verfasserin aut Chunling Li verfasserin aut Weidong Wang verfasserin aut Jørgen Frøkiær verfasserin aut Lene N. Nejsum verfasserin aut Tae-Hwan Kwon verfasserin aut Rikke Nørregaard verfasserin aut In Frontiers in Physiology Frontiers Media S.A., 2011 10(2019) (DE-627)631498788 (DE-600)2564217-0 1664042X nnns volume:10 year:2019 https://doi.org/10.3389/fphys.2019.00948 kostenfrei https://doaj.org/article/41b4fc3c33514cb58d811ce65c2fe4cd kostenfrei https://www.frontiersin.org/article/10.3389/fphys.2019.00948/full kostenfrei https://doaj.org/toc/1664-042X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2019
allfieldsGer	10.3389/fphys.2019.00948 doi (DE-627)DOAJ033661197 (DE-599)DOAJ41b4fc3c33514cb58d811ce65c2fe4cd DE-627 ger DE-627 rakwb eng QP1-981 Stine Julie Tingskov verfasserin aut Vasopressin-Independent Regulation of Aquaporin-2 by Tamoxifen in Kidney Collecting Ducts 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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-β 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. Aquaporin-2 inner medullary collecting duct tamoxifen unilateral ureteral obstruction vasopressin Physiology Hyo-Jung Choi verfasserin aut Mikkel R. Holst verfasserin aut Shan Hu verfasserin aut Chunling Li verfasserin aut Weidong Wang verfasserin aut Jørgen Frøkiær verfasserin aut Lene N. Nejsum verfasserin aut Tae-Hwan Kwon verfasserin aut Rikke Nørregaard verfasserin aut In Frontiers in Physiology Frontiers Media S.A., 2011 10(2019) (DE-627)631498788 (DE-600)2564217-0 1664042X nnns volume:10 year:2019 https://doi.org/10.3389/fphys.2019.00948 kostenfrei https://doaj.org/article/41b4fc3c33514cb58d811ce65c2fe4cd kostenfrei https://www.frontiersin.org/article/10.3389/fphys.2019.00948/full kostenfrei https://doaj.org/toc/1664-042X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2019
allfieldsSound	10.3389/fphys.2019.00948 doi (DE-627)DOAJ033661197 (DE-599)DOAJ41b4fc3c33514cb58d811ce65c2fe4cd DE-627 ger DE-627 rakwb eng QP1-981 Stine Julie Tingskov verfasserin aut Vasopressin-Independent Regulation of Aquaporin-2 by Tamoxifen in Kidney Collecting Ducts 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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-β 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. Aquaporin-2 inner medullary collecting duct tamoxifen unilateral ureteral obstruction vasopressin Physiology Hyo-Jung Choi verfasserin aut Mikkel R. Holst verfasserin aut Shan Hu verfasserin aut Chunling Li verfasserin aut Weidong Wang verfasserin aut Jørgen Frøkiær verfasserin aut Lene N. Nejsum verfasserin aut Tae-Hwan Kwon verfasserin aut Rikke Nørregaard verfasserin aut In Frontiers in Physiology Frontiers Media S.A., 2011 10(2019) (DE-627)631498788 (DE-600)2564217-0 1664042X nnns volume:10 year:2019 https://doi.org/10.3389/fphys.2019.00948 kostenfrei https://doaj.org/article/41b4fc3c33514cb58d811ce65c2fe4cd kostenfrei https://www.frontiersin.org/article/10.3389/fphys.2019.00948/full kostenfrei https://doaj.org/toc/1664-042X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2019
language	English
source	In Frontiers in Physiology 10(2019) volume:10 year:2019
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format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Aquaporin-2 inner medullary collecting duct tamoxifen unilateral ureteral obstruction vasopressin Physiology
isfreeaccess_bool	true
container_title	Frontiers in Physiology
authorswithroles_txt_mv	Stine Julie Tingskov @@aut@@ Hyo-Jung Choi @@aut@@ Mikkel R. Holst @@aut@@ Shan Hu @@aut@@ Chunling Li @@aut@@ Weidong Wang @@aut@@ Jørgen Frøkiær @@aut@@ Lene N. Nejsum @@aut@@ Tae-Hwan Kwon @@aut@@ Rikke Nørregaard @@aut@@
publishDateDaySort_date	2019-01-01T00:00:00Z
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topic_title	QP1-981 Vasopressin-Independent Regulation of Aquaporin-2 by Tamoxifen in Kidney Collecting Ducts Aquaporin-2 inner medullary collecting duct tamoxifen unilateral ureteral obstruction vasopressin
topic	misc QP1-981 misc Aquaporin-2 misc inner medullary collecting duct misc tamoxifen misc unilateral ureteral obstruction misc vasopressin misc Physiology
topic_unstemmed	misc QP1-981 misc Aquaporin-2 misc inner medullary collecting duct misc tamoxifen misc unilateral ureteral obstruction misc vasopressin misc Physiology
topic_browse	misc QP1-981 misc Aquaporin-2 misc inner medullary collecting duct misc tamoxifen misc unilateral ureteral obstruction misc vasopressin misc Physiology
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title	Vasopressin-Independent Regulation of Aquaporin-2 by Tamoxifen in Kidney Collecting Ducts
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title_full	Vasopressin-Independent Regulation of Aquaporin-2 by Tamoxifen in Kidney Collecting Ducts
author_sort	Stine Julie Tingskov
journal	Frontiers in Physiology
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author_browse	Stine Julie Tingskov Hyo-Jung Choi Mikkel R. Holst Shan Hu Chunling Li Weidong Wang Jørgen Frøkiær Lene N. Nejsum Tae-Hwan Kwon Rikke Nørregaard
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author-letter	Stine Julie Tingskov
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title_sort	vasopressin-independent regulation of aquaporin-2 by tamoxifen in kidney collecting ducts
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title_auth	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-β 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.
abstractGer	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-β 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.
abstract_unstemmed	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-β 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.
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title_short	Vasopressin-Independent Regulation of Aquaporin-2 by Tamoxifen in Kidney Collecting Ducts
url	https://doi.org/10.3389/fphys.2019.00948 https://doaj.org/article/41b4fc3c33514cb58d811ce65c2fe4cd https://www.frontiersin.org/article/10.3389/fphys.2019.00948/full https://doaj.org/toc/1664-042X
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