The changes of cell cycle regulators which may trigger G0 to G1 transition during liver regeneration have been examined. In vivo thymidine uptake indicated that S phase began about 18 h and the peak of DNA synthesis appeared from 21 to 24 h after partial hepatectomy. Various time-points from G0 to mid-S-phase were selected within 24 h after partial hepatectomy and the expression levels of cyclins, cyclin-dependent kinase (Cdk) and cyclindependent kinase inhibitors (CKIs) were examined by Northern and Western analysis. Both cyclin D1 mRNA and protein increased at 15 h after operation. Cyclin E mRNA was first detected at 12 h and continued to increase until 21 h, whereas expression of cyclin B mRNA was first observed at 21 h. Expression of Cdk4 mRNA in normal rat liver was clearly detectable, increased significantly at 9 h after resection, and remained increased up to 24 h. On the other hand, an increase in Cdk4 protein was observed as early as 3 h after the surgery and reached plateau at 18 h. We next examined expression of CKIs which may regulate activity of cyclin/Cdk complex during liver regeneration. p 2 7K I P 1 protein was detected in normal rat liver whereas p21C I P 1 protein was not. Expression of p 2 1C I P 1 protein appeared as early as 3 h and continued to increase up to 21 h. Expression of p27KIP1 protein, however, increased slightly until 24 h.
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Cho, H., Lim, I. & Lee, JH. Changes in the expression of cell cycle regulators during rat liver regeneration after partial hepatectomy. Exp Mol Med 28, 187–191 (1996). https://doi.org/10.1038/emm.1996.29
- cell cycle
- cyclin-dependent kinases
- cyclin-dependent kinase inhibitors
- partial hepatectomy