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

Détails

ID Serval
serval:BIB_3109692321ED
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Nuclear Factor I-C acts as a regulator of hepatocyte proliferation at the onset of liver regeneration.
Périodique
Liver International
Auteur(s)
Edelmann S., Fahrner R., Malinka T., Song B.H., Stroka D., Mermod N.
ISSN
1478-3231 (Electronic)
ISSN-L
1478-3223
Statut éditorial
Publié
Date de publication
2015
Volume
35
Numéro
4
Pages
1185-1194
Langue
anglais
Résumé
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.
Mots-clé
Animals, Cell Proliferation, Feedback, Physiological, Gene Expression Regulation, Genotype, Hepatectomy/methods, Hepatocyte Growth Factor/genetics, Hepatocyte Growth Factor/metabolism, Liver/metabolism, Liver/pathology, Liver Regeneration, Male, Mice, Inbred C57BL, Mice, Knockout, NFI Transcription Factors/deficiency, NFI Transcription Factors/genetics, Phenotype, Plasminogen Activator Inhibitor 1/genetics, Plasminogen Activator Inhibitor 1/metabolism, Signal Transduction, Time Factors, Transforming Growth Factor beta1/genetics, Transforming Growth Factor beta1/metabolism, Urokinase-Type Plasminogen Activator/genetics, Urokinase-Type Plasminogen Activator/metabolism
Pubmed
Web of science
Création de la notice
21/01/2016 11:20
Dernière modification de la notice
20/08/2019 13:16
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