title: HGF-induced DNA synthesis in hepatocytes is suppressed by p38.
abstract: Previous studies in rat hepatocytes have shown that the MEK/ERK, PI3K/Akt and p38 pathways are all involved in the activation of DNA synthesis by EGF and that sustained activation of MEK/ERK is required. Here, we show that although HGF stimulated DNA synthesis and activated signaling in the same manner as EGF, the contribution of the signaling pathways to the induction of DNA synthesis differed. While HGF-induced DNA synthesis was dependent on MEK/ERK, with no significant contribution from PI3K/Akt, p38 suppressed HGF-induced DNA synthesis. The p38 inhibitor SB203580 increased HGF-induced DNA synthesis and enhanced the phosphorylation of ERK. In contrast, SB203580 decreased EGF-induced ERK phosphorylation. This suggests that p38 has distinct effects on DNA synthesis induced by EGF and HGF. Due to differential regulation of signaling through the MEK/ERK pathway, p38 acts as an enhancer of EGF-induced DNA synthesis and as a suppressor of HGF-induced DNA synthesis.
authors.affiliation: a Department of Pharmacology , Institute of Clinical Medicine, University of Oslo and Oslo University Hospital , Oslo , Norway.
authors.forename: Monica
authors.initials: M
authors.lastname: Aasrum
authors.affiliation: b Department of Oral Biology and Department of Paediatric Dentistry and Behavioural Science , Faculty of Dentistry, University of Oslo , Oslo , Norway , and.
authors.forename: Ingvild J
authors.initials: IJ
authors.lastname: Brusevold
authors.affiliation: a Department of Pharmacology , Institute of Clinical Medicine, University of Oslo and Oslo University Hospital , Oslo , Norway.
authors.forename: Thoralf
authors.initials: T
authors.lastname: Christoffersen
authors.affiliation: a Department of Pharmacology , Institute of Clinical Medicine, University of Oslo and Oslo University Hospital , Oslo , Norway.|c Department of Pharmaceutical Biosciences , School of Pharmacy, University of Oslo , Oslo , Norway.
authors.forename: G Hege
authors.initials: GH
authors.lastname: Thoresen
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004261:DNA Replication; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D022781:Hepatocytes / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D008297:Male; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D017228:Hepatocyte Growth Factor; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580
keywords: EGF; HGF p38; Hepatocytes