{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T21:38:27Z","timestamp":1779399507114,"version":"3.53.1"},"reference-count":41,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,23]],"date-time":"2020-04-23T00:00:00Z","timestamp":1587600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Lithium chloride (LiCl) is a widely used drug for the treatment of bipolar disorders, but as a side effect, 40% of the patients develop diabetes insipidus. LiCl affects the activity of the glycogen synthase kinase 3 (GSK3), and mice deficient for GSK3\u03b2 showed a reduction in the urine concentration capability. The cellular and molecular mechanisms are not fully understood. We used primary cultured inner medullary collecting duct cells to analyze the underlying mechanisms. LiCl and the inhibitor of GSK3 (SB216763) induced a decrease in the aquaporin-2 (Aqp2) protein level. LiCl induced downregulation of Aqp2 mRNA expression while SB216763 had no effect and TWS119 led to increase in expression. The inhibition of the lysosomal activity with bafilomycin or chloroquine prevented both LiCl- and SB216763-mediated downregulation of Aqp2 protein expression. Bafilomycin and chloroquine induced the accumulation of Aqp2 in lysosomal structures, which was prevented in cells treated with dibutyryl cyclic adenosine monophosphate (dbcAMP), which led to phosphorylation and membrane localization of Aqp2. Downregulation of Aqp2 was also evident when LiCl was applied together with dbcAMP, and dbcAMP prevented the SB216763-induced downregulation. We showed that LiCl and SB216763 induce downregulation of Aqp2 via different mechanisms. While LiCl also affected the mRNA level, SB216763 induced lysosmal degradation. Specific GSK3\u03b2 inhibition had an opposite effect, indicating a more complex regulatory mechanism.<\/jats:p>","DOI":"10.3390\/cells9041060","type":"journal-article","created":{"date-parts":[[2020,4,23]],"date-time":"2020-04-23T10:46:22Z","timestamp":1587638782000},"page":"1060","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Lithium Chloride and GSK3 Inhibition Reduce Aquaporin-2 Expression in Primary Cultured Inner Medullary Collecting Duct Cells Due to Independent Mechanisms"],"prefix":"10.3390","volume":"9","author":[{"given":"Marc","family":"Kaiser","sequence":"first","affiliation":[{"name":"Medizinische Klinik D, Experimentelle Nephrologie, Universit\u00e4tsklinikum M\u00fcnster, 48143 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bayram","family":"Edemir","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hematology and Oncology, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1073\/pnas.92.4.1013","article-title":"Vasopressin increases water permeability of kidney collecting duct by inducing translocation of aquaporin-CD water channels to plasma membrane","volume":"92","author":"Nielsen","year":"1995","journal-title":"Proc. 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