Ilowski, Maren and Putz, Christine and Weiss, Thomas S. and Brand, Stephan and Jauch, Karl-Walter and Hengstler, Jan G. and Thasler, Wolfgang Erwin (2010) Augmenter of liver regeneration causes different kinetics of ERK1/2 and Akt/PKB phosphorylation than EGF and induces hepatocyte proliferation in an EGF receptor independent and liver specific manner. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 394 (4). pp. 915-920. ISSN 0006-291X, 1090-2104
Full text not available from this repository. (Request a copy)Abstract
Background/Aim: Augmenter of liver regeneration (ALR) is a potent growth factor which supports liver regeneration in experimental animals. The aim of this study was to compare proliferation as well as the kinetics of ERK1/2 and Akt/PKB phosphorylation by recombinant human ALR (rhALR) and EGF in human hepatocytes and extrahepatic cells. Methods: Kinetics of ERK1/2 and Akt/PKB phosphorylation were determined in primary human hepatocytes (phh) after stimulation with rhALR and EGF. Induction of proliferation was analyzed in phh and several cell lines of hepatic and extrahepatic origin by the MTT and [H-3]-thymidine assay. Results: The kinetics of ERK phosphorylation showed clear differences, whereby rhALR caused a transient and EGF a permanent increase during the observation period of 60 min. For both, Akt and ERK phosphorylation, EGF caused a faster effect with maximal levels observed already after 2 min, whereas rhALR caused maximal phosphorylation between 10 and 15 min. Using the EGF receptor inhibitor AG1478 we provide evidence of an EGF receptor independent induction of proliferation by rhALR. Furthermore, rhALR induced proliferation only in phh and the human liver derived cell lines HepG2 and Chang. In contrast, EGF enhanced proliferation in all analyzed cell types including cell lines of colon, bronchial, pancreatic and gastric origin (SW480, BC1, L36PL and GC1). Conclusion: rhALR and EGF induce different kinetics of ERK and Akt phosphorylation in human hepatocytes. The mitogenic effect of rhALR is liver specific and seems to be at least partially independent from EGF receptor mediated signaling. (C) 2010 Elsevier Inc. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HEPATIC STIMULATOR SUBSTANCE; GROWTH-FACTOR; CELL-SURVIVAL; HEPATOTROPHIC FACTOR; ACTINOMYCIN-D; HEPATOPOIETIN; EXPRESSION; APOPTOSIS; PANCREAS; KINASE; Augmenter of liver regeneration; Human hepatocytes; Liver regeneration; AKT/PKB; ERK1/2; Liver specificity |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 03 Aug 2020 06:12 |
| Last Modified: | 03 Aug 2020 06:12 |
| URI: | https://pred.uni-regensburg.de/id/eprint/24820 |
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