Nuclear Factor I‐C acts as a regulator of hepatocyte proliferation at the onset of liver regeneration. (25th October 2014)

• Record Type: Journal Article
• Authors: Edelmann, Simone; Fahrner, René; Malinka, Thomas; Song, Bryan H.; Stroka, Deborah; Mermod, Nicolas
• Is Part Of: Liver international. Volume 35:Number 4(2015:Apr.)
• Page Start: 1185
• Page End: 1194
• Publication Date: 2014-10-25
• Subjects: Liver -- Periodicals; Liver -- Diseases -- Periodicals; 616.362
• DOI: 10.1111/liv.12697
• Languages: English
• ISSNs: 1478-3223

Abstract

<abstract abstract-type="main" id="liv12697-abs-0001"> <title>Abstract</title> <sec id="liv12697-sec-0001" sec-type="section"> <title>Background & Aims</title> <p>Knockout studies of the murine Nuclear Factor I‐C (NFI‐C) 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 (PH) is a well‐established regenerative model whereby changes elicited in hepatocytes lead to their rapid and phased proliferation. Although NFI‐C is highly expressed in the liver, no hepatic function was yet established for this transcription factor. This study aimed to determine whether NFI‐C may play a role in hepatocyte proliferation and liver regeneration.</p> </sec> <sec id="liv12697-sec-0002" sec-type="section"> <title>Methods</title> <p>Liver regeneration and cell proliferation pathways following two‐thirds PH were investigated in NFI‐C knockout (ko) and wild‐type (wt) mice.</p> </sec> <sec id="liv12697-sec-0003" sec-type="section"> <title>Results</title> <p>We show that the absence of NFI‐C impaired hepatocyte proliferation because of plasminogen activator I (PAI‐1) overexpression and the subsequent suppression of urokinase plasminogen activator (uPA) activity and hepatocyte growth factor (HGF) signalling, a potent hepatocyte mitogen. This indicated that NFI‐C first acts to promote hepatocyte proliferation at the onset of liver regeneration in wt mice. The subsequent transient down regulation of <italic>NFI‐C</italic>, as can be explained by a self‐regulatory feedback loop with transforming growth factor beta 1 (TGF‐ß1), may limit the number of hepatocytes entering the first wave of cell division and/or prevent late initiations of mitosis.</p> </sec> <sec id="liv12697-sec-0004" sec-type="section"> <title>Conclusion</title> <p>NFI‐C acts as a regulator of the phased hepatocyte proliferation during liver regeneration.</p> </sec> </abstract>