Brg1 promotes liver regeneration after partial hepatectomy via regulation of cell cycle.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
20 02 2019
20 02 2019
Historique:
received:
05
07
2018
accepted:
21
12
2018
entrez:
22
2
2019
pubmed:
23
2
2019
medline:
17
9
2020
Statut:
epublish
Résumé
Brahma-related gene 1 (Brg1), a catalytic subunit of the SWItch/Sucrose Non-Fermentable (SWI/SNF) complex, is known to be involved in proliferative cell processes. Liver regeneration is initiated spontaneously after injury and leads to a strong proliferative response. In this study, a hepatocyte-specific Brg1 gene knockout mouse model was used to analyse the role of Brg1 in liver regeneration by performing a 70% partial hepatectomy (PH). After PH, Brg1 was significantly upregulated in wildtype mice. Mice with hepatocyte-specific Brg1 gene knockout showed a significantly lower liver to body weight ratio 48 h post-PH concomitant with a lower hepatocellular proliferation rate compared to wildtype mice. RNA sequencing demonstrated that Brg1 controlled hepatocyte proliferation through the regulation of the p53 pathway and several cell cycle genes. The data of this study reveal a crucial role of Brg1 for liver regeneration by promoting hepatocellular proliferation through modulation of cell cycle genes and, thus, identify Brg1 as potential target for therapeutic approaches.
Identifiants
pubmed: 30787318
doi: 10.1038/s41598-019-38568-w
pii: 10.1038/s41598-019-38568-w
pmc: PMC6382836
doi:
Substances chimiques
Nuclear Proteins
0
Transcription Factors
0
Tumor Suppressor Protein p53
0
Smarca4 protein, mouse
EC 3.6.1.-
DNA Helicases
EC 3.6.4.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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