Figure 2.

Model prediction of qualitative input–output experiments (a) and inhibition results (b–e). (a) Input–output validation: model predictions agreed with published experimental observations for 31 out of 39 (80%) of the input–output responses measured in rat or human PAAFs. Intermediate and phenotypic output results are organized by input stimulus, where the bolded node names indicate experimental results that were measured in vivo. (b–e) Inhibition validation: results of the PAAF model are compared with the results of inhibition experiments in cultured rat PAAFs reported by Zhang et al. (b–d) [76] and He et al. (e) [77]. Each model prediction was normalized to the baseline condition obtained when all inputs were 0.25. Stimulation with TGFβ and TNFα were simulated by increasing these inputs to 0.475 and 0.375, respectively, to be consistent with the experimental protocol. The effects of the ERK inhibitor (T+U), p38 inhibitor (T+SB) and ROS scavenger (NAC) were simulated by decreasing y_max for those nodes from 1.0 to 0.3, 0.05 and 0, respectively, consistent with the published reports [83,84]. (Online version in colour.)