ArticleWorld journal of hepatology2020
Cyclin-dependent kinase inhibitors p21 and p27 function as critical regulators of liver regeneration following 90% hepatectomy in the rat.
Article in World journal of hepatology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed, 4 citations in OpenAlex.
- Therapeutic priming of liver regeneration: from mechanisms toFrontiers in transplantation · 2026Review
- Bile Acid Overload Induced by Bile Duct and Portal Vein Ligation Improves Survival after Staged Hepatectomy in Rats.Current medical science · 2023Article
- Adapalene Inhibits Prostate Cancer Cell ProliferationFrontiers in pharmacology · 2022Article
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Authors and funding
6 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundLiver reduction is the main curative treatment for primary liver cancer, but its use remains limited as liver regeneration requires a minimum of 30% functional parenchyma.
aimTo study the dynamics of the liver regeneration process and consequent behavior of cell cycle regulators in rats after extended hepatectomy (90%) and postoperative glucose infusions.
methodsPost-hepatectomy liver failure was triggered in 84 Wistar rats by reducing their liver mass by 90%. The animals received a post-operative glucose infusion and were randomly assigned to two groups: One to investigate the survival rate and the other for biochemical analyses. Animals that underwent laparotomy or 70% hepatectomy were used as controls. Blood and liver samples were collected on postoperative days 1 to 7. Liver morphology, function, and regeneration were studied with histology, immunohistochemistry, and western blotting.
resultsPostoperative mortality after major resection reached 20% and 55% in the first 24 h and 48 h, respectively, with an overall total of 70% 7 d after surgery. No apparent signs of apoptotic cell death were detected in the extended hepatectomy rat livers, but hepatocytes displaying a clear cytoplasm and an accumulation of hyaline material testified to changes affecting their functional activities. Liver regeneration started properly, as early events initiating cell proliferation occurred within the first 3 h, and the G1 to S transition was detected in less than 12 h. However, a rise in p27 (Kip1) followed by p21 (Waf1/Cip1) cell cycle inhibitor levels led to a delayed S phase progression and mitosis. Overall, liver regeneration in rats with a 90% hepatectomy was delayed by 24 h and associated with a delayed onset and lower peak magnitude of hepatocellular deoxyribonucleic acid synthesis.
conclusionThis work highlights the critical importance of the cyclin/cyclin-dependent kinase inhibitors of the Cip/Kip family in regulating the liver regeneration timeline following extended hepatectomy.
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