Fig. 1

Influence map of the signaling and gene regulatory networks (GRN) implemented in the model. Red, T-ended arrows represent inhibitory influences and black arrows represent activating influences. On the signaling side, growth factors and pro-inflammatory cytokines are represented by green rectangular nodes, receptors are yellow triangles, kinase proteins are yellow hexagons and other signaling proteins are yellow ellipses. Transcription factors (TFs) are represented in blue both in the signaling network and the GRN. In addition, target genes are represented by yellow rectangles in the GRN, and TFs might also be targets of other TFs in the GRN. In this image, each biological component is represented by a gene in the GRN and a protein in the signaling network, except for the ones that are not involved in one of the subnetworks (e.g., NKX3.2 only plays a role in the GRN while COL-II and COL-X do not have upstream and downstream influences in the protein signaling network). Network images were designed with Cell Designer