Primary mouse hepatocytes for systems biology approaches: a standardized in vitro system for modelling of signal transduction pathways
Abstract
Complex cellular networks regulate regeneration, detoxification and differentiation of hepatocytes. By combining experimental data with mathematical modelling, systems biology holds great promises to elucidate the key regulatory mechanisms involved and predict targets for efficient intervention. For the generation of high-quality quantitative data suitable for mathematical modelling a standardised in vitro system is essential. Therefore the authors developed standard operating procedures for the preparation and cultivation of primary mouse hepatocytes. To reliably monitor the dynamic induction of signalling pathways, the authors established starvation conditions and evaluated the extent of starvation-associated stress by quantifying several metabolic functions of cultured primary hepatocytes, namely activities of glutathione-S-transferase, glutamine synthetase, CYP3A as well as secretion of lactate and urea into the culture medium. Establishment of constant metabolic activities after an initial decrease compared with freshly isolated hepatocytes showed that the cultured hepatocytes achieve a new equilibrium state that was not affected by our starving conditions. To verify the highly reproducible dynamic activation of signalling pathways in the in vitro system, the authors examined the JAK-STAT, SMAD, PI3 kinase, MAP kinase, NF-kappaB and Wnt/beta-catenin signalling pathways. For the induction of gp130, JAK1 and STAT3 phosphorylation IL6 was used, whereas TGFbeta was applied t…
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Primary mouse hepatocyte isolation was performed in a standardized way according to Klingmuller et al. (2006) or according to the refined protocol described by Huard et al. (2012).
“Primary mouse hepatocyte isolation was performed in a standardized way according to Klingmuller et al. (2006) or according to the refined protocol described by Huard et al. (2012).”
From Model Based Targeting of IL-6-Induced Inflammatory Responses in Cultured Primary Hepatocytes to Improve Application of the JAK Inhibitor Ruxolitinib (2017) · cites this paper as Klingmuller et al. (2006)
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- Authors
- Klingmüller, U., Bauer, A., Bohl, S., Nickel, P. J., Breitkopf, K., Dooley, S., Zellmer, S., Kern, C., Merfort, I., Sparna, T., Donauer, J., Walz, G., Geyer, M., Kreutz, C., Hermes, M., Götschel, F., Hecht, A., Walter, D., Egger, L., Neubert, K., Borner, C., Brulport, M., Schormann, W., Sauer, C., Baumann, F., Preiss, R., MacNelly, S., Godoy, P., Wiercinska, E., Ciuclan, L., Edelmann, J., Zeilinger, K., Heinrich, M., Zanger, U. M., Gebhardt, R., Maiwald, T., Heinrich, R., Timmer, J., von Weizsäcker, F., & Hengstler, J. G.
- Affiliations
- Leipzig University (DE)
- German Cancer Research Center (DE)
- Heidelberg University (DE)
- University of Freiburg (DE)
- University Medical Center Freiburg (DE)
- ORCID
- Venue
- IEE Proceedings - Systems Biology
- Published
- 2006
- Volume
- 153
- Issue
- 6
- Pages
- 433
- ISSN
- 1741-2471 (ISSN-L)
- OpenAlex
- W2028286333
- Cited by
- 127
- References
- 1
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 1 · 2021: 6 · 2020: 6 · 2019: 3 · 2018: 3 · 2017: 6 · 2016: 10 · 2015: 9 · 2014: 12 · 2013: 8 · 2012: 14
- FWCI
- 6.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Systems Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bundesministerium für Bildung und Forschung
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Keywords
- hepatocyte culture, standard operating procedures, signaling pathways, starvation stress, glutathione S-transferase, glutamine synthetase, CYP3A, JAK/STAT signaling, Smad signaling, PI3-kinase, mitogen-activated protein kinase, NF-κB, Wnt/β-catenin signaling, GSK-3β inhibition, hepatocyte growth factor, interleukin-6, TGF-beta
- MeSH terms
- Animals, Computer Simulation, Models, Biological, Multienzyme Complexes, Signal Transduction, Cytokines, Hepatocytes, Models, Animal, Systems Biology, Mice
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