{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T07:43:52Z","timestamp":1785743032391,"version":"3.56.0"},"reference-count":51,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,10,25]],"date-time":"2014-10-25T00:00:00Z","timestamp":1414195200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006390","name":"University of Lausanne","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006390","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>Knockout studies of the murine Nuclear Factor I\u2010C (<jats:styled-content style=\"fixed-case\">NFI<\/jats:styled-content>\u2010C) transcription factor revealed abnormal skin wound healing and growth of its appendages, suggesting a role in controlling cell proliferation in adult regenerative processes. Liver regeneration following partial hepatectomy (<jats:styled-content style=\"fixed-case\">PH<\/jats:styled-content>) is a well\u2010established regenerative model whereby changes elicited in hepatocytes lead to their rapid and phased proliferation. Although <jats:styled-content style=\"fixed-case\">NFI<\/jats:styled-content>\u2010C is highly expressed in the liver, no hepatic function was yet established for this transcription factor. This study aimed to determine whether <jats:styled-content style=\"fixed-case\">NFI<\/jats:styled-content>\u2010C may play a role in hepatocyte proliferation and liver regeneration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Liver regeneration and cell proliferation pathways following two\u2010thirds <jats:styled-content style=\"fixed-case\">PH<\/jats:styled-content> were investigated in <jats:styled-content style=\"fixed-case\">NFI<\/jats:styled-content>\u2010C knockout (ko) and wild\u2010type (wt) mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We show that the absence of NFI\u2010C impaired hepatocyte proliferation because of plasminogen activator I (PAI\u20101) overexpression and the subsequent suppression of urokinase plasminogen activator (<jats:styled-content style=\"fixed-case\">uPA<\/jats:styled-content>) activity and hepatocyte growth factor (HGF) signalling, a potent hepatocyte mitogen. This indicated that NFI\u2010C first acts to promote hepatocyte proliferation at the onset of liver regeneration in wt mice. The subsequent transient down regulation of <jats:italic>NFI\u2010C<\/jats:italic>, as can be explained by a self\u2010regulatory feedback loop with transforming growth factor beta 1 (TGF\u2010\u00df1), may limit the number of hepatocytes entering the first wave of cell division and\/or prevent late initiations of mitosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">NFI<\/jats:styled-content>\u2010C acts as a regulator of the phased hepatocyte proliferation during liver regeneration.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.12697","type":"journal-article","created":{"date-parts":[[2014,10,8]],"date-time":"2014-10-08T07:04:20Z","timestamp":1412751860000},"page":"1185-1194","source":"Crossref","is-referenced-by-count":18,"title":["Nuclear Factor I\u2010C acts as a regulator of hepatocyte proliferation at the onset of liver 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