Modularized Smad-regulated TGFβ signaling pathway

The transforming Growth Factor β (TGFβ) signaling pathway is a prominent regulatory signaling pathway controlling various important cellular processes. TGFβ signaling can be induced by several factors including ionizing radiation. The pathway is regulated in a negative feedback loop through promoting the nuclear import of the regulatory Smads and a subsequent expression of inhibitory Smad7, that forms ubiquitin ligase with Smurf2, targeting active TGFβ receptors for degradation. In this work, we proposed a mathematical model to study the Smad-regulated TGFβ signaling pathway. By modularization, we are able to analyze mathematically each component subsystem and recover the nonlinear dynamics of the entire network system. Meanwhile the excitability, a common feature observed in the biological systems, in the TGFβ signaling pathway is discussed and supported as well by numerical simulation, indicating the robustness of the model.

► A mathematical model of Smad regulated TFGβ signaling pathway is presented. ► The model modularized for TFG activation by radiation and inhibition by Smad7. ► Stability analysis of each module is conducted to reveal the entire system stability. ► Excitability is studied and revealed by mathematical and numerical analysis.