TGF-beta and IL-6 family signalling crosstalk: an integrated model
Details
Publication Year 2017-06, Volume 35, Issue #2-3, Page 100-124
Journal Title
Growth Factors
Publication Type
Journal Article
Abstract
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.
Publisher
Taylor & Francis
WEHI Research Division(s)
Structural Biology; Systems Biology And Personalised Medicine
PubMed ID
28948853
Rights Notice
Refer to copyright notice on published article.


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