Mathematical modeling of canonical and non-canonical NF-κB pathways in TNF stimulation

Ji, Bing; Zhang, Yao; Zhen, Changqing; Fagan, Michael J.; Yang, Qing

Abstract

Background and objective: NF-κB can be activated by the canonical and non-canonical pathways. These two pathways interplay via the TRAF1|NIK complex after stimulation by TNF. However existing mathematical models of two pathways are inadequate. In this context, an improved mathematical model is constructed to simulate these two pathways and their coupling stimulated by TNF. Methods: A schematic description of two NF-κB pathways and their relation after TNF stimulation is constructed at first. Then twenty-eight ordinary differential equations are utilized to build the mathematical model. Model equations are solved via the ordinary differential equation solver (ode23). Results: The proposed model firstly reconstructs the changes in concentrations of NF-κB pathway related biochemical factors with time, and further investigates the underlying mechanism of interaction between two pathways through the TRAF1|NIK complex after stimulation. Conclusions: The model is validated through good agreement between simulation results and published experimental observations. This study helps to well understand the canonical and non-canonical pathways and their interaction. It also provides a potential tool to investigate how the dysregulated pathways act in pathological conditions.

Citation

Ji, B., Zhang, Y., Zhen, C., Fagan, M. J., & Yang, Q. (2020). Mathematical modeling of canonical and non-canonical NF-κB pathways in TNF stimulation. Computer Methods and Programs in Biomedicine, 196, Article 105677. https://doi.org/10.1016/j.cmpb.2020.105677

• Journal Article Type: Article
• Acceptance Date: Jul 22, 2020
• Online Publication Date: Jul 30, 2020
• Publication Date: 2020-11
• Deposit Date: Aug 14, 2020
• Publicly Available Date: Jul 31, 2021
• Journal: Computer Methods and Programs in Biomedicine
• Print ISSN: 0169-2607
• Electronic ISSN: 1872-7565
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 196
• Article Number: 105677
• DOI: https://doi.org/10.1016/j.cmpb.2020.105677
• Keywords: NF-κB; Canonical pathway; Non-canonical pathway; Coupling; Mathematical modeling
• Public URL: https://hull-repository.worktribe.com/output/3557688
• Publisher URL: https://www.sciencedirect.com/science/article/abs/pii/S0169260720315108?via%3Dihub
• Additional Information: This article is maintained by: Elsevier; Article Title: Mathematical modeling of canonical and non-canonical NF-κB pathways in TNF stimulation; Journal Title: Computer Methods and Programs in Biomedicine; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.cmpb.2020.105677; Content Type: article; Copyright: © 2020 Elsevier B.V. All rights reserved.