Transcription factor CREM coordinates the timing of hepatocyte proliferation in the regenerating liver
Abstract
The liver regenerates upon partial hepatectomy (PH) as terminally differentiated hepatocytes undergo a tremendous proliferative process. CREM gene expression is powerfully induced during liver regeneration. We show that cell proliferation is significantly reduced upon PH in CREM−/− mice. There is a reduction in DNA synthesis, in the number of mitosis and of phosphorylated histone H3-positive cells. The post-PH proliferation peak is delayed by 10 hr, indicating an altered hepatocyte cell cycle. Expression of cyclins A, B, D1, E, and cdc2, of c-fos and tyrosine aminotransferase is deregulated. CREM mutation results in delayed S-phase entry, impairing the synchronization of proliferation.
Footnotes
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↵1 On leave from the Institute of General Pathology, University of Perugia, Policlinico Monteluce, Perugia, Italy. These authors contributed equally to the work.
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↵2 Corresponding author.
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E-MAIL paolosc{at}igbmc.u-strasbg.fr; FAX 33 388 653246.
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- Received September 10, 1998.
- Accepted October 15, 1998.
- Cold Spring Harbor Laboratory Press
