Transcriptional and Post-Transcriptional Regulation of Thrombospondin-1 Expression: A Computational Model
Fig 9
Global sensitivity analysis of model parameters.
Global sensitivity analysis of parameters that control (A) the area under curve (AUC) of HIF-1 dimer in a span of 48 hours in 2% oxygen, (B) AUC of activated SMAD2-SMAD4 complex in nucleus in a span of 24 hours upon 2.5 ng/ml TGFβ stimulation, (C) AUC of TSP-1 in a span of 24 hours under the condition of normoxia plus Myc hyperactivity and (D) AUC of TSP-1 in a span of 24 hours upon 2.5 ng/ml TGFβ stimulation plus hypoxia (2% oxygen). (A-D) Rate descriptions—kf1: HIF-1α translocation into nucleus; kf2: HIF-1α binds FIH complex; kf4: oxygen binds FIH complex; kf7: HIF-1α binds PHD complex; kf8: oxygen binds PHD complex; kf11: HIF1α-OH-FIH dissociation; kf13: HIF1α-OH-PHD dissociation; kf18: TTP synthesis; kf19: HIF-1α binds HIF-1β; vm1: HIF-1α synthesis; vm2: HIF-2α synthesis; vm3: Myc synthesis; vm5: let-7 synthesis; vm6: MXI-1 synthesis; vm7: miR-18a synthesis; vm9: LIN28B synthesis; vm11: PSAP synthesis; vm13: p53 synthesis; vm18: AGO1 synthesis; vm19: Dicer synthesis; vm20: TSP-1 synthesis; kf66: TGFβR internalization; kf72: TGFβR degradation; kf73: TGFβ binds its receptor; kf74: receptor dimer binds R-SMAD; kf75: R-SMAD phosphorylation; kf76: R-SMAD translocation into nucleus; kf77: phosphorylated R-SMAD (pR-SMAD) binds SMAD4; kf78: pR-SMAD-SMAD4 complex translocation into nucleus; kf79: SMAD4 translocation into nucleus; kf82: pSMAD2-SMAD4 dephosphorylation; kf89: SMAD7 sequesters activated R-SMAD; vm27: TGFβ-mediated calcium influx; vm29: NFAT dephosphorylation; vm32: SMAD7 synthesis; vm34: SMAD4 degradation; vm36: SMAD4 synthesis.