{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:40:23Z","timestamp":1791286823227,"version":"4.1.0"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"51","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,12,18]]},"abstract":"<jats:p>\n                    Hepatocyte nuclear factor-1\u03b2 (HNF-1\u03b2) is a Pit-1, Oct-1\/2, Unc-86 (POU) homeodomain-containing transcription factor expressed in the kidney, liver, pancreas, and other epithelial organs. Mutations of HNF-1\u03b2 cause maturity-onset diabetes of the young, type 5 (MODY5), which is characterized by early-onset diabetes mellitus and congenital malformations of the kidney, pancreas, and genital tract. Knockout of HNF-1\u03b2 in the mouse kidney results in cyst formation. However, the signaling pathways and transcriptional programs controlled by HNF-1\u03b2 are poorly understood. Using genome-wide chromatin immunoprecipitation and DNA microarray (ChIP-chip) and microarray analysis of mRNA expression, we identified\n                    <jats:italic>SOCS3<\/jats:italic>\n                    (suppressor of cytokine signaling-3) as a previously unrecognized target gene of HNF-1\u03b2 in the kidney. HNF-1\u03b2 binds to the\n                    <jats:italic>SOCS3<\/jats:italic>\n                    promoter and represses\n                    <jats:italic>SOCS3<\/jats:italic>\n                    transcription. The expression of\n                    <jats:italic>SOCS3<\/jats:italic>\n                    is increased in HNF-1\u03b2 knockout mice and in renal epithelial cells expressing dominant-negative mutant HNF-1\u03b2. Increased levels of SOCS-3 inhibit HGF-induced tubulogenesis by decreasing phosphorylation of Erk and STAT-3. Conversely, knockdown of SOCS-3 in renal epithelial cells expressing dominant-negative mutant HNF-1\u03b2 rescues the defect in HGF-induced tubulogenesis by restoring phosphorylation of Erk and STAT-3. Thus, HNF-1\u03b2 regulates tubulogenesis by controlling the levels of SOCS-3 expression. Manipulating the levels of SOCS-3 may be a useful therapeutic approach for human diseases induced by HNF-1\u03b2 mutations.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0705957104","type":"journal-article","created":{"date-parts":[[2007,12,12]],"date-time":"2007-12-12T20:54:44Z","timestamp":1197492884000},"page":"20386-20391","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":63,"title":["Mutations of HNF-1\u03b2 inhibit epithelial morphogenesis through dysregulation of SOCS-3"],"prefix":"10.1073","volume":"104","author":[{"given":"Zhendong","family":"Ma","sequence":"first","affiliation":[{"name":"Departments of *Internal Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimei","family":"Gong","sequence":"additional","affiliation":[{"name":"Departments of *Internal Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishal","family":"Patel","sequence":"additional","affiliation":[{"name":"Departments of *Internal Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney M.","family":"Karner","sequence":"additional","affiliation":[{"name":"Departments of *Internal Medicine,"},{"name":"Molecular Biology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyne","family":"Fischer","sequence":"additional","affiliation":[{"name":"Gene Expression, Development and Disease Laboratory, Department of Developmental Biology, Centre National de la Recherche Scientifique URA 2578\/Pasteur Institute, 75724 Paris Cedex 15, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Hiesberger","sequence":"additional","affiliation":[{"name":"Departments of *Internal Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Carroll","sequence":"additional","affiliation":[{"name":"Departments of *Internal Medicine,"},{"name":"Molecular Biology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Pontoglio","sequence":"additional","affiliation":[{"name":"Gene Expression, Development and Disease Laboratory, Department of Developmental Biology, Centre National de la Recherche Scientifique URA 2578\/Pasteur Institute, 75724 Paris Cedex 15, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Igarashi","sequence":"additional","affiliation":[{"name":"Departments of *Internal Medicine,"},{"name":"Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390; 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