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TGF-beta and IL-6 family signalling crosstalk: an integrated model


Khatibi, S; Babon, J; Wagner, J; Manton, JH; Tan, CW; Zhu, HJ; Wormald, S; Burgess, AW
2017-06
Growth Factors
Journal Article
35
2-3
100-124
Mathematical models for TGF-beta and IL-6 signalling have been linked, providing a platform for analyzing the crosstalk between the systems. An integrated IL-6:TGF-beta model was developed via a reduced set of reaction equations which incorporate both feedback loops and appropriate time-delays for transcription and translation processes. The model simulates stable, robust and realistic responses to both ligands. Pulsatile (multiple pulses) inputs for both TGF-beta and IL-6 have been simulated to investigate the effects of each ligand on the sensitivity, equilibrium and dynamic responses of the integrated signalling system. In our simulations the crosstalk between constant IL-6 and TGF-beta signalling via SMAD7 does not appear to be sufficient to render the cells resistant to TGF-beta inhibition. However, the simulations predict that pulsatile IL-6 stimulation would increase SMAD7 levels substantially and consequentially, lead to resistance to TGF-beta. The model also allows the prediction of the integrated signalling pathway responses to the mutation of key components, e.g. Gp130 F/F.
Taylor & Francis
Structural Biology; Systems Biology and Personalised Medicine
10.1080/08977194.2017.1363746
28948853
Refer to copyright notice on published article.

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Creation Date 2017-10-16 02:00:02 Last Modified 2017-10-16 04:41:55