{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:01:33Z","timestamp":1790737293749,"version":"4.1.0"},"reference-count":54,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2017,10]]},"abstract":"\n The transcription factor hepatocyte nuclear factor\u20131\n \u03b2<\/jats:italic>\n (HNF-1\n \u03b2<\/jats:italic>\n ) is essential for normal kidney development and function. Inactivation of HNF-1\n \u03b2<\/jats:italic>\n in mouse kidney tubules leads to early-onset cyst formation and postnatal lethality. Here, we used Pkhd1\/Cre mice to delete HNF-1\n \u03b2<\/jats:italic>\n specifically in renal collecting ducts (CDs). CD-specific HNF-1\n \u03b2<\/jats:italic>\n mutant mice survived long term and developed slowly progressive cystic kidney disease, renal fibrosis, and hydronephrosis. Compared with wild-type littermates, HNF-1\n \u03b2<\/jats:italic>\n mutant mice exhibited polyuria and polydipsia. Before the development of significant renal structural abnormalities, mutant mice exhibited low urine osmolality at baseline and after water restriction and administration of desmopressin. However, mutant and wild-type mice had similar plasma vasopressin and solute excretion levels. HNF-1\n \u03b2<\/jats:italic>\n mutant kidneys showed increased expression of aquaporin-2 mRNA but mislocalized expression of aquaporin-2 protein in the cytoplasm of CD cells. Mutant kidneys also had decreased expression of the UT-A urea transporter and collectrin, which is involved in apical membrane vesicle trafficking. Treatment of HNF-1\n \u03b2<\/jats:italic>\n mutant mIMCD3 cells with hypertonic NaCl inhibited the induction of osmoregulated genes, including\n Nr1h4<\/jats:italic>\n , which encodes the transcription factor FXR that is required for maximal urinary concentration. Chromatin immunoprecipitation and sequencing experiments revealed HNF-1\n \u03b2<\/jats:italic>\n binding to the\n Nr1h4<\/jats:italic>\n promoter in wild-type kidneys, and immunoblot analysis revealed downregulated expression of FXR in HNF-1\n \u03b2<\/jats:italic>\n mutant kidneys. These findings reveal a novel role of HNF-1\n \u03b2<\/jats:italic>\n in osmoregulation and identify multiple mechanisms, whereby mutations of HNF-1\n \u03b2<\/jats:italic>\n produce defects in urinary concentration.\n <\/jats:p>","DOI":"10.1681\/asn.2016101095","type":"journal-article","created":{"date-parts":[[2017,5,15]],"date-time":"2017-05-15T20:25:33Z","timestamp":1494879933000},"page":"2887-2900","source":"Crossref","is-referenced-by-count":46,"title":["Hepatocyte Nuclear Factor\u20131\u03b2 Regulates Urinary Concentration and Response to Hypertonicity"],"prefix":"10.1681","volume":"28","author":[{"given":"Karam","family":"Aboudehen","sequence":"first","affiliation":[{"name":"Medicine and"},{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lama","family":"Noureddine","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas;"},{"name":"Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Cobo-Stark","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Avdulov","sequence":"additional","affiliation":[{"name":"Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shayan","family":"Farahani","sequence":"additional","affiliation":[{"name":"Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micah D.","family":"Gearhart","sequence":"additional","affiliation":[{"name":"Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel G.","family":"Bichet","sequence":"additional","affiliation":[{"name":"Medicine and"},{"name":"Molecular and Integrative Physiology, Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Pontoglio","sequence":"additional","affiliation":[{"name":"Department of Development, Reproduction and Cancer, Institut Cochin, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U1016\/Centre National de la Recherche Scientifique Unit\u00e9 Mixte de Recherche 8104, Universit\u00e9 Paris-Descartes, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishal","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Igarashi","sequence":"additional","affiliation":[{"name":"Medicine and"},{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2017,5,15]]},"reference":[{"key":"B1-20230819","doi-asserted-by":"crossref","first-page":"1944","DOI":"10.1111\/j.1523-1755.2005.00625.x","article-title":"Roles of HNF-1beta in kidney development and congenital cystic diseases.","volume":"68","author":"Igarashi","year":"2005","journal-title":"Kidney Int"},{"key":"B2-20230819","doi-asserted-by":"crossref","first-page":"10578","DOI":"10.1074\/jbc.M414121200","article-title":"Role of the hepatocyte nuclear factor-1beta (HNF-1beta) C-terminal domain in Pkhd1 (ARPKD) gene transcription and renal cystogenesis.","volume":"280","author":"Hiesberger","year":"2005","journal-title":"J Biol Chem"},{"key":"B3-20230819","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1681\/ASN.2008020238","article-title":"HNF-1beta regulates transcription of the PKD modifier gene Kif12.","volume":"20","author":"Gong","year":"2009","journal-title":"J Am Soc Nephrol"},{"key":"B4-20230819","doi-asserted-by":"crossref","first-page":"20386","DOI":"10.1073\/pnas.0705957104","article-title":"Mutations of HNF-1beta inhibit epithelial morphogenesis through dysregulation of SOCS-3.","volume":"104","author":"Ma","year":"2007","journal-title":"Proc Natl Acad Sci USA"},{"key":"B5-20230819","doi-asserted-by":"crossref","first-page":"F839","DOI":"10.1152\/ajprenal.00128.2002","article-title":"Regulation of kidney-specific Ksp-cadherin gene promoter by hepatocyte nuclear factor-1beta.","volume":"283","author":"Bai","year":"2002","journal-title":"Am J Physiol Renal 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regulates organic solute transporters alpha and beta in the adrenal gland, kidney, and intestine.","volume":"47","author":"Lee","year":"2006","journal-title":"J Lipid Res"},{"key":"B47-20230819","doi-asserted-by":"crossref","first-page":"e105930","DOI":"10.1371\/journal.pone.0105930","article-title":"Genome-wide binding and transcriptome analysis of human farnesoid X receptor in primary human hepatocytes.","volume":"9","author":"Zhan","year":"2014","journal-title":"PLoS One"},{"key":"B48-20230819","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1074\/jbc.M115.694323","article-title":"Farnesoid X receptor protects against kidney injury in uninephrectomized obese mice.","volume":"291","author":"Gai","year":"2016","journal-title":"J Biol Chem"},{"key":"B49-20230819","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1515\/bmc-2012-0001","article-title":"The role of hyperosmotic stress in inflammation and 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Potential physiological role.","volume":"79","author":"Bichet","year":"1987","journal-title":"J Clin Invest"},{"key":"B53-20230819","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/nmeth.3252","article-title":"Orchestrating high-throughput genomic analysis with bioconductor.","volume":"12","author":"Huber","year":"2015","journal-title":"Nat Methods"},{"key":"B54-20230819","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2.","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol"}],"container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/00001751-201710000-00012","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T19:29:07Z","timestamp":1786130947000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/00001751-201710000-00012"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,15]]},"references-count":54,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2017]]}},"URL":"https:\/\/doi.org\/10.1681\/asn.2016101095","relation":{},"ISSN":["1046-6673","1533-3450"],"issn-type":[{"value":"1046-6673","type":"print"},{"value":"1533-3450","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5,15]]}}}