HBEGF and pulmonary arterial hypertension: An imbalance between M1 and M2 macrophages has been noted in monocyte-derived macrophages from PAH patients.170 Previous research indicated that JNK phosphorylation promotes M1 polarization while inhibiting M2 polarization in macrophages.171 However, Zhang et al. discovered that tumor M2 macrophages over-expressing NOX4 exhibited increased JNK activity, leading to the expression and release of HB-EGF, which promotes non-small cell lung cancer proliferation in vitro.172 This suggests that the regulatory role of JNK in macrophage activation may also be relevant in the context of PAH.