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regulation of water homeostasis, and we have previously shown that tamoxifen (TAM), a selective estrogen receptor modulator (SERM), affects the regulation of aquaporin (AQP)-2. In this study, we investigated the effect of TAM on the expression and localization of AQP3 in collecting ducts using various animal, tissue, and cell models. The impact of TAM on AQP3 regulation was studied in rats subjected to 7 days of unilateral ureteral obstruction (UUO), with the rats fed a lithium-containing diet to induce nephrogenic diabetes insipidus (NDI), as well as in human precision-cut kidney slices (PCKS). Moreover, intracellular trafficking of AQP3 after TAM treatment was investigated in Madin-Darby Canine Kidney (MDCK) cells stably expressing AQP3. In all models, the expression of AQP3 was evaluated by Western blotting, immunohistochemistry and qPCR. TAM administration attenuated UUO-induced downregulation of AQP3 and affected the localization of AQP3 in both the UUO model and the lithium-induced NDI model. In parallel, TAM also affected the expression profile of other basolateral proteins, including AQP4 and Na\/K-ATPase. In addition, TGF-\u03b2 and TGF-\u03b2+TAM treatment affected the localization of AQP3 in stably transfected MDCK cells, and TAM partly attenuated the reduced AQP3 expression in TGF-\u03b2 exposed human tissue slices. These findings suggest that TAM attenuates the downregulation of AQP3 in a UUO model and a lithium-induced NDI model and affects the intracellular localization in the collecting ducts.<\/jats:p>","DOI":"10.3390\/cells12081140","type":"journal-article","created":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T01:35:00Z","timestamp":1681349700000},"page":"1140","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Tamoxifen Affects Aquaporin-3 Expression and Subcellular Localization in Rat and Human Renal Collecting Ducts"],"prefix":"10.3390","volume":"12","author":[{"given":"Stine Julie","family":"Tingskov","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariagrazia","family":"D\u2019Agostino","sequence":"additional","affiliation":[{"name":"Department of Bioscience, Biotechnologies and Environment, University of Bari, 70125 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fr\u00e9d\u00e9ric H.","family":"Login","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8890-0278","authenticated-orcid":false,"given":"Grazia","family":"Tamma","sequence":"additional","affiliation":[{"name":"Department of Bioscience, Biotechnologies and Environment, University of Bari, 70125 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4368-8821","authenticated-orcid":false,"given":"Lene N.","family":"Nejsum","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0580-373X","authenticated-orcid":false,"given":"Rikke","family":"N\u00f8rregaard","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, Denmark"},{"name":"Department of Renal Medicine, Aarhus University Hospital, 8200 Aarhus N, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1056\/NEJMra1404726","article-title":"Molecular physiology of water balance","volume":"372","author":"Knepper","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_2","first-page":"185","article-title":"Aquaglyceroporins in the kidney: Present state of knowledge and prospects","volume":"67","author":"Michalek","year":"2016","journal-title":"J. Physiol. Pharmacol. Off. J. Pol. Physiol. Soc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1177\/1933719113518992","article-title":"Hormonal changes during menopause and the impact on fluid regulation","volume":"21","author":"Stachenfeld","year":"2014","journal-title":"Reprod. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1113\/jphysiol.2003.046920","article-title":"Oestrogen effects on urine concentrating response in young women","volume":"552","author":"Stachenfeld","year":"2003","journal-title":"J. Physiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"F305","DOI":"10.1152\/ajprenal.00685.2014","article-title":"Estradiol regulates AQP2 expression in the collecting duct: A novel inhibitory role for estrogen receptor \u03b1","volume":"309","author":"Cheema","year":"2015","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"F1020","DOI":"10.1152\/ajprenal.00604.2017","article-title":"Tamoxifen attenuates development of lithium-induced nephrogenic diabetes insipidus in rats","volume":"314","author":"Tingskov","year":"2018","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"948","DOI":"10.3389\/fphys.2019.00948","article-title":"Vasopressin-independent regulation of aquaporin-2 by tamoxifen in kidney collecting ducts","volume":"10","author":"Tingskov","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s00345-011-0674-3","article-title":"Changes in aquaporin (AQP)2 and AQP3 expression in ovariectomized rat urinary bladder: Potential implication of water permeability in urinary bladder","volume":"30","author":"Kim","year":"2012","journal-title":"World J. Urol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1093\/humrep\/dey290","article-title":"Aquaporin-3 mediates ovarian steroid hormone-induced motility of endometrial epithelial cells","volume":"33","author":"Cui","year":"2018","journal-title":"Hum. Reprod."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"12484","DOI":"10.1038\/srep12484","article-title":"Identification of Estrogen Response Element in Aquaporin-3 Gene that Mediates Estrogen-induced Cell Migration and Invasion in Estrogen Receptor-positive Breast Cancer","volume":"5","author":"Huang","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_11","first-page":"431","article-title":"Molecular Mechanisms of Selective Estrogen Receptor Modulator (SERM) Action","volume":"295","author":"Dutertre","year":"2000","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"F1066","DOI":"10.1152\/ajprenal.00090.2002","article-title":"Downregulation of renal aquaporins in response to unilateral ureteral obstruction","volume":"284","author":"Li","year":"2003","journal-title":"Am. J. Physiol.-Ren. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"F552","DOI":"10.1152\/ajprenal.2000.279.3.F552","article-title":"Altered expression of renal AQPs and Na+transporters in rats with Lithium-induced NDI","volume":"279","author":"Kwon","year":"2000","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"111003","DOI":"10.1016\/j.biopha.2020.111003","article-title":"Tamoxifen attenuates renal fibrosis in human kidney slices and rats subjected to unilateral ureteral obstruction","volume":"133","author":"Tingskov","year":"2021","journal-title":"Biomed. Pharm."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"903","DOI":"10.3389\/fphys.2018.00903","article-title":"Tamoxifen Decreases Lithium-Induced Natriuresis in Rats With Nephrogenic Diabetes Insipidus","volume":"9","author":"Tingskov","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_16","first-page":"1546","article-title":"Aldosterone-mediated apical targeting of ENaC subunits is blunted in rats with streptozotocin-induced diabetes mellitus","volume":"23","author":"Lebeck","year":"2007","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.ab.2012.10.010","article-title":"Stain-Free technology as a normalization tool in Western blot analysis","volume":"433","author":"Kunz","year":"2013","journal-title":"Anal. Biochem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"C654","DOI":"10.1152\/ajpcell.00186.2017","article-title":"Ectopic expression of aquaporin-5 in noncancerous epithelial MDCK cells changes cellular morphology and actin fiber formation without inducing epithelial-to-mesenchymal transition","volume":"314","author":"Jensen","year":"2018","journal-title":"Am. J. Physiol. Cell. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5243","DOI":"10.1242\/jcs.02633","article-title":"Distribution and dynamics of Lamp1-containing endocytic organelles in fibroblasts deficient in BLOC-3","volume":"118","author":"Nazarian","year":"2005","journal-title":"J. Cell Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 years of image analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.trsl.2015.11.007","article-title":"Precision-cut human kidney slices as a model to elucidate the process of renal fibrosis","volume":"170","author":"Stribos","year":"2016","journal-title":"Transl. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e13291","DOI":"10.1111\/apha.13291","article-title":"Activation of the prostaglandin E2 EP2 receptor attenuates renal fibrosis in unilateral ureteral obstructed mice and human kidney slices","volume":"227","author":"Jensen","year":"2019","journal-title":"Acta Physiol. Scand."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1152\/physrev.2001.81.1.345","article-title":"Sodium-Potassium-Adenosinetriphosphatase-Dependent Sodium Transport in the Kidney: Hormonal Control","volume":"81","author":"Doucet","year":"2001","journal-title":"Physiol. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s12931-017-0544-7","article-title":"The roles and regulation of the actin cytoskeleton, intermediate filaments and microtubules in smooth muscle cell migration","volume":"18","author":"Tang","year":"2017","journal-title":"Respir. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/bs.vh.2019.08.016","article-title":"Estrogen regulates aquaporin-2 expression in the kidney","volume":"112","author":"Tingskov","year":"2020","journal-title":"Vitam. Horm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"C298","DOI":"10.1152\/ajpcell.00356.2005","article-title":"Polarized trafficking of the aquaporin-3 water channel is mediated by an NH2-terminal sorting signal","volume":"290","author":"Rai","year":"2006","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s10549-014-3017-4","article-title":"Tamoxifen through GPER upregulates aromatase expression: A novel mechanism sustaining tamoxifen-resistant breast cancer cell growth","volume":"146","author":"Catalano","year":"2014","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"C952","DOI":"10.1152\/ajpcell.00266.2003","article-title":"Changes in cellular composition of kidney collecting duct cells in rats with lithium-induced NDI","volume":"286","author":"Christensen","year":"2004","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1002\/JLB.2VMA0818-328R","article-title":"Tamoxifen induces toxicity, causes autophagy, and partially reverses dexamethasone resistance in Jurkat T cells","volume":"105","author":"Maycotte","year":"2019","journal-title":"J. Leukoc. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ruby, M., Gifford, C.C., Pandey, R., Raj, V.S., Sabbisetti, V.S., and Ajay, A.K. (2023). Autophagy as a Therapeutic Target for Chronic Kidney Disease and the Roles of TGF-beta1 in Autophagy and Kidney Fibrosis. Cells, 12.","DOI":"10.3390\/cells12030412"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"122","DOI":"10.2133\/dmpk.DMPK-11-RV-084","article-title":"Pharmacogenomics of tamoxifen: Roles of drug metabolizing enzymes and transporters","volume":"27","author":"Kiyotani","year":"2012","journal-title":"Drug Metab. Pharmacokinet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1124\/jpet.104.065607","article-title":"Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: Prominent roles for CYP3A and CYP2D6","volume":"310","author":"Desta","year":"2004","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/j.1476-5381.1980.tb10912.x","article-title":"Evidence for the metabolic activation of non-steroidal antioestrogens: A study of structure-activity relationships","volume":"71","author":"Allen","year":"1980","journal-title":"Br. J. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5624","DOI":"10.1111\/bph.12864","article-title":"Simulation with cells in vitro of tamoxifen treatment in premenopausal breast cancer patients with different CYP2D6 genotypes","volume":"171","author":"Maximov","year":"2014","journal-title":"Br. J. Pharmacol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/8\/1140\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:14:54Z","timestamp":1760123694000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/8\/1140"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,12]]},"references-count":34,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["cells12081140"],"URL":"https:\/\/doi.org\/10.3390\/cells12081140","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,12]]}}}