Besides, the expression of macrophage migration inhibitory factor (MIF), a critical proinflammatory mediator, was also upregulated in the lung tissues from pulmonary hypertensive rats subjected to chronic hypoxic exposure (Fig. 6, middle, hormonal responses).336 This study further revealed that MIF facilitated hypoxia-induced PASMCs proliferation through activating the ERK1/2 and JNK pathways, without the involvement of p38, thus contributing to HPVR and pulmonary hypertension. This evidence concerns the gene MAPK8 and pulmonary arterial hypertension.