{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:06:42Z","timestamp":1790665602019,"version":"4.1.0"},"reference-count":48,"publisher":"American Physiological Society","issue":"1","funder":[{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research)","doi-asserted-by":"publisher","award":["VICI 016.130.668"],"award-info":[{"award-number":["VICI 016.130.668"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002997","name":"Nierstichting (Dutch Kidney Foundation)","doi-asserted-by":"publisher","award":["Kolff 14OKG17"],"award-info":[{"award-number":["Kolff 14OKG17"]}],"id":[{"id":"10.13039\/501100002997","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2018,7,1]]},"abstract":"<jats:p> Mutations in hepatocyte nuclear factor 1\u03b2 (HNF1\u03b2) cause autosomal dominant tubulointerstitial kidney disease (ADTKD-HNF1\u03b2), and patients tend to develop renal cysts, maturity-onset diabetes of the young (MODY), and suffer from electrolyte disturbances, including hypomagnesemia, hypokalemia, and hypocalciuria. Previous HNF1\u03b2 research focused on the renal distal convoluted tubule (DCT) to elucidate the ADTKD-HNF1\u03b2 electrolyte phenotype, although 70% of Mg<jats:sup>2+<\/jats:sup> is reabsorbed in the thick ascending limb of Henle\u2019s loop (TAL). An important regulator of Mg<jats:sup>2+<\/jats:sup> reabsorption in the TAL is the calcium-sensing receptor (CaSR). This study used several methods to elucidate the role of HNF1\u03b2 in electrolyte reabsorption in the TAL. HNF1\u03b2 ChIP-seq data revealed a conserved HNF1\u03b2 binding site in the second intron of the CaSR gene. Luciferase-promoter assays displayed a 5.8-fold increase in CaSR expression when HNF1\u03b2 was present. Expression of the HNF1\u03b2 p.Lys156Glu mutant, which prevents DNA binding, abolished CaSR expression. Hnf1\u03b2 knockdown in an immortalized mouse kidney TAL cell line (MKTAL) reduced expression of the CaSR and Cldn14 (claudin 14) by 56% and 48%, respectively, while Cldn10b expression was upregulated 5.0-fold. These results were confirmed in a kidney-specific HNF1\u03b2 knockout mouse, which exhibited downregulation of the Casr by 81%. Cldn19 and Cldn10b expression levels were also decreased by 37% and 83%, respectively, whereas Cldn3 was upregulated by 4.6-fold. In conclusion, HNF1\u03b2 is a transcriptional activator of the CaSR. Consequently, patients with HNF1\u03b2 mutations may have reduced CaSR activity in the kidney, which could explain cyst progression and hyperabsorption of Ca<jats:sup>2+<\/jats:sup> and Mg<jats:sup>2+<\/jats:sup> in the TAL resulting in hypocalciuria. <\/jats:p>","DOI":"10.1152\/ajprenal.00601.2017","type":"journal-article","created":{"date-parts":[[2018,3,21]],"date-time":"2018-03-21T10:57:08Z","timestamp":1521629828000},"page":"F27-F35","source":"Crossref","is-referenced-by-count":24,"title":["Transcription factor HNF1\u03b2 regulates expression of the calcium-sensing receptor in the thick ascending limb of the kidney"],"prefix":"10.1152","volume":"315","author":[{"given":"Andreas","family":"Kompatscher","sequence":"first","affiliation":[{"name":"Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2372-8486","authenticated-orcid":false,"given":"Jeroen H. 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