A mechanistic integrative computational model of macrophage polarization: Implications in human pathophysiology
Fig 4
Hypoxia promotes M1 and M2 marker expression.
Model simulation and literature experimental data from macrophages on hypoxia-induced (A) time-course stabilization of HIF-1α and (B) HIF-2α under 3% O2 [75, 76], (C) sustained stabilization of HIF-1/2α at 24 h under 0.5% O2 [77], (D) upregulation of iNOS and (E) Arg-1 proteins at 8 h under 1% O2 [78], (F) increase in TNFα secretion at 24 h under 0.3% O2 [79], (G) increase in IFN-γ secretion over time under 1% O2 [47], (H) increase in VEGF secretion at 24 h under 1% O2 [80], and (I) inhibition of miR-93 abundance at 12 h under 2% O2 [53]. (J) Enforced overexpression of miR-93 (see also S4G Fig) leads to decreased IFN-γ secretion at 12 h under 2% O2 [53]. (A-J) All literature data are measured in macrophage cell lines and results are for protein levels unless noted otherwise. Y-axes show normalized expression respectively (A, B: simulations and data are normalized to the maximum expression; C: normalized to the expression at 24 h under hypoxia; D-I: normalized to the normoxic/time 0 expression; J: normalized to the hypoxia-induced expression at 12 h without miR-93 mimic treatment). S–simulation, D–literature data, Utr–normoxia/untreated, Trd–treated with miR-93 mimic, Hyp–hypoxia, O2 –oxygen.