HMGB1 affects the development of pulmonary arterial hypertension via RAGE.

OBJECTIVE: To investigate the effect of high-mobility group box 1 (HMGB1) on the proliferation, migration and inflammatory response of human pulmonary artery smooth muscle cells (HPASMCs) and human pulmonary artery endothelial cells (HPAECs) through the receptor for advanced glycation end products (RAGE) and to investigate the mechanism of action underlying the effect of HMGB1 on pulmonary arterial hypertension.

MATERIALS AND METHODS: The effect of HMGB1 on the proliferation of the two cell types was examined using the MTT assay under environmental hypoxia (incubation with 1.5% oxygen) to simulate the condition of pulmonary arterial hypertension in the body. The effect of HMGB1 on HPAEC migration was observed using the scratch assay. The effect of HMGB1 on the inflammatory mediators IL-6 and CXCL8 in the two cell types was assessed using qPCR (Real-time Quantitative PCR) and ELISA, and the RAGE mRNA and protein expression levels were also examined.

RESULTS: Hypoxia promoted the proliferation of both cell types but inhibited the migration of HPAECs. HMGB1 had no obvious effect on the proliferation and migration of the cells. Both hypoxia and HMGB1 promoted the expression of the pro-inflammatory factors IL-6 and CXCL8. HMGB1 significantly promoted RAGE expression compared to the normal control group.

CONCLUSIONS: HMGB1 affects the functions of HPASMCs and HPAECs through RAGE and may affect the course of pulmonary arterial hypertension.