Transcriptional and Post-Transcriptional Regulation of Thrombospondin-1 Expression: A Computational Model
Fig 3
Model optimization against experimental data in ECs.
(A-D) Experimental measurement and model simulation of phosphorylated SMAD1 and SMAD2 protein in response to 1 ng/ml TGFβ treatment in BAECs: (A) normalized phosphorylated SMAD1 protein level without CHX treatment, (B) normalized phosphorylated SMAD2 protein level without CHX treatment, (C) normalized phosphorylated SMAD1 protein level with CHX treatment, (D) normalized phosphorylated SMAD2 protein level with CHX treatment. The time-course experimental data from Valdimarsdottir et al. and simulation results are both normalized with respect to the corresponding peak value [71]. (E) Experimental data from Goumans et al. and model-generated dose response curve of total phosphorylated SMAD2 protein measured at 60 minutes after TGFβ treatment. X-axis is in log scale. Values are normalized against the maximum of each dataset [72]. (F) HIF-1α protein stabilization and (G) AGO1 protein downregulation are observed in HUVECs in hypoxia (2% O2) by Chen et al [23]. (H-I) Dicer protein is downregulated by hypoxia (1% O2) in HUVECs; hypoxia results in accumulation of HIF-2α protein in human dermal microvascular ECs from Ho et al [59]. (J) P53 protein expression is induced in hypoxic conditions (1% O2) in HUVECs; experimental data from Lee et al [73]. (K) TSP-1 protein expression is increased in hypoxia in HUVECs (2.7% O2); data from Phelan et al [16]. (L) TSP-1 protein expression is induced in human pulmonary aortic endothelial cells in response to 24 hours of hypoxia; data from Labrousse-Arias et al [14]. (A-L) Results (data-point values and simulations) are normalized against the maximum (or the normoxic baseline values) in each dataset. Quantification of experimental data from the literature is done in ImageJ following standard protocols.