Division Systems Biology of Signal Transduction, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Biochem J. 2022 Jun 30;479(12):1361-1374. doi: 10.1042/BCJ20210548.
In health and disease, liver cells are continuously exposed to cytokines and growth factors. While individual signal transduction pathways induced by these factors were studied in great detail, the cellular responses induced by repeated or combined stimulations are complex and less understood. Growth factor receptors on the cell surface of hepatocytes were shown to be regulated by receptor interactions, receptor trafficking and feedback regulation. Here, we exemplify how mechanistic mathematical modelling based on quantitative data can be employed to disentangle these interactions at the molecular level. Crucial is the analysis at a mechanistic level based on quantitative longitudinal data within a mathematical framework. In such multi-layered information, step-wise mathematical modelling using submodules is of advantage, which is fostered by sharing of standardized experimental data and mathematical models. Integration of signal transduction with metabolic regulation in the liver and mechanistic links to translational approaches promise to provide predictive tools for biology and personalized medicine.
在健康和疾病状态下，肝细胞持续暴露于细胞因子和生长因子中。尽管这些因子所诱导的单个信号转导通路已得到深入研究，但对于反复或联合刺激所诱导的细胞反应，其复杂性和了解程度则较低。已证实，肝细胞表面的生长因子受体受到受体相互作用、受体运输和反馈调节的调控。在此，我们举例说明了如何基于定量数据的机制数学建模可用于在分子水平上阐明这些相互作用。关键是在数学框架内基于定量纵向数据进行机制分析。在这种多层次信息中，使用子模块逐步进行数学建模具有优势，这得益于标准化实验数据和数学模型的共享。将信号转导与肝脏中的代谢调控相结合，并与转化方法建立机制联系，有望为生物学和个性化医疗提供预测工具。
