ArticlePloS one2013
Induction of p53-dependent p21 limits proliferative activity of rat hepatocytes in the presence of hepatocyte growth factor.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed, 6 citations in OpenAlex.
- Integrated analysis of microbiome and transcriptome reveals the mechanisms underlying the chlorogenic acid-mediated attenuation of oxidative stress and systemic inflammatory responses via gut-liver axis in post-peaking laying hens.Journal of animal science and biotechnology · 2025Article
- Cell cycle regulation in NAFLD: when imbalanced metabolism limits cell division.Hepatology international · 2020Review
- Senescent Hepatocytes in Decompensated Liver Show Reduced UPRCellular and molecular gastroenterology and hepatology · 2019Article
- Inhibitor of p53-p21 pathway induces the differentiation of human umbilical cord derived mesenchymal stem cells into cardiomyogenic cells.Cytotechnology · 2016Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHepatocyte growth factor (HGF), a potent mitogen for hepatocytes, enhances hepatocyte function without stimulating proliferation, depending on the physiological conditions. p53, a transcription factor, suppresses the cell proliferation by expressing p21(WAF1/CIP1) in various tissues.
aimTo investigate the mechanism through which the hepatocytes maintain mitotically quiescent even in the presence of HGF.
methodsWe studied the relationship between p53 and p21 expression and the effect of p53-p21 axis on hepatocyte proliferation in primary cultured rat hepatocytes stimulated by HGF. Hepatic p21 levels are determined serially after partial hepatectomy or sham operation in rats.
resultsDNA synthesis was markedly increased by HGF addition in rat hepatocytes cultured at low density but not at high density. Cellular p53 levels increased in the hepatocytes cultured at both the densities. p21 levels were increased and correlated with cellular p53 levels in hepatocytes cultured at high density but not at low density. When the activity of p53 was suppressed by a chemical inhibitor for p53, cellular p21 levels were reduced, and DNA synthesis was increased. Similarly, p21 antisense oligonucleotide increased the DNA synthesis. In rats after partial hepatectomy, transient elevation of hepatic p21 levels was observed. In contrast, in sham-operated rats, hepatic p21 levels were increased on sustained time scales.
conclusionp53-related induction of p21 may suppress hepatocyte proliferation in the presence of HGF in the setting that mitogenic activity of HGF is not elicitable.
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