Nrf2 is essential for timely M phase entry of replicating hepatocytes during liver regeneration.
Am J Physiol Gastrointest Liver Physiol
; 308(4): G262-8, 2015 Feb 15.
Article
in En
| MEDLINE
| ID: mdl-25524062
ABSTRACT
The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) regulates various cellular activities, including redox balance, detoxification, metabolism, autophagy, proliferation, and apoptosis. Several studies have demonstrated that Nrf2 regulates hepatocyte proliferation during liver regeneration. The aim of this study was to investigate how Nrf2 modulates the cell cycle of replicating hepatocytes in regenerating livers. Wild-type and Nrf2 null mice were subjected to 2/3 partial hepatectomy (PH) and killed at multiple time points for various analyses. Nrf2 null mice exhibited delayed liver regrowth, although the lost liver mass was eventually restored 7 days after PH. Nrf2 deficiency did not affect the number of hepatocytes entering the cell cycle but did delay hepatocyte mitosis. Mechanistically, the lack of Nrf2 resulted in increased mRNA and protein levels of hepatic cyclin A2 when the remaining hepatocytes were replicating in response to PH. Moreover, Nrf2 deficiency in regenerating livers caused dysregulation of Wee1, Cdc2, and cyclin B1 mRNA and protein expression, leading to decreased Cdc2 activity. Thus, Nrf2 is required for timely M phase entry of replicating hepatocytes by ensuring proper regulation of cyclin A2 and the Wee1/Cdc2/cyclin B1 pathway during liver regeneration.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell Division
/
Hepatocytes
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NF-E2-Related Factor 2
/
Liver
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Liver Regeneration
/
Mitosis
Limits:
Animals
Language:
En
Journal:
Am J Physiol Gastrointest Liver Physiol
Journal subject:
FISIOLOGIA
/
GASTROENTEROLOGIA
Year:
2015
Document type:
Article