HMGB1 and pulmonary arterial hypertension: In human PASMCs pre-treated with ET-1, BMPR2 expression is reduced, while BMP2 binds to BMPR1B, thereby activating the p38 pathway to drive PASMC proliferation, with the effect amplified under pathological conditions.353 In PASMCs from MCT-PAH rat models, HMGB1 triggers ERK1/2 signaling, leading to Drp1 phosphorylation and mitochondrial fragmentation, which promotes autophagy activation, resulting in BMPR2 degradation, ID1 downregulation, and PASMC proliferation/migration.354 These pathways appear to operate in parallel rather than as a direct upstream-downstream relationship.