Nuclear Factor I-C acts as a regulator of hepatocyte proliferation at the onset of liver regeneration

Edelmann, Simone; Fahrner, René; Malinka, Thomas; Song, Bryan H.; Keogh-Stroka, Deborah M.; Mermod, Nicolas (2014). Nuclear Factor I-C acts as a regulator of hepatocyte proliferation at the onset of liver regeneration. Liver international, 35(4), pp. 1185-1194. Blackwell Munksgaard 10.1111/liv.12697

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BACKGROUND & AIMS: 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. METHODS: Liver regeneration and cell proliferation pathways following two-thirds PH were investigated in NFI-C knockout (ko) and wild-type (wt) mice. RESULTS: 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 NFI-C, 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. CONCLUSION: NFI-C acts as a regulator of the phased hepatocyte proliferation during liver regeneration.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Viszeralchirurgie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Viszeralchirurgie

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine

UniBE Contributor:

Fahrner, René; Malinka, Thomas and Keogh-Stroka, Deborah M.

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1478-3223

Publisher:

Blackwell Munksgaard

Language:

English

Submitter:

Lilian Karin Smith-Wirth

Date Deposited:

21 Apr 2015 13:55

Last Modified:

11 May 2016 22:26

Publisher DOI:

10.1111/liv.12697

PubMed ID:

25293436

Uncontrolled Keywords:

NFI; PAI-1; partial hepatectomy; proliferation; TGF-ß1; tissue regeneration; urokinase

BORIS DOI:

10.7892/boris.66953

URI:

https://boris.unibe.ch/id/eprint/66953

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