CXCR7 promotes pulmonary vascular remodeling via targeting p38/MMP2 pathway in pulmonary arterial hypertension

• DOI: 10.21037/jtd-24-331
• Publication Date: 2024-04-29T07:01:45Z
• Authors: Jingjing Xu; Shuai Miao; Tianjun Wu; Chunxiao Hu; Dongxiao Huang; Xin Zhang
• Keywords: Hypoxia; MMP2

Background: A hallmark feature of pulmonary arterial hypertension (PAH) is the excessive proliferation artery smooth muscle cells (PASMCs) in arteries. The exact role C-X-C motif chemokine ligand 12 (CXCL12)/chemokine receptor type 7 (CXCR7) PASMCs remains unknown. Methods: In this study, we examined expression profile CXCL12/CXCR7 both hypoxic rats and PASMCs. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) was used to measure level Enzyme-linked immunosorbent assay (ELISA) western blotting assays were applied investigate protein related molecules. Results: We found that a high CXCR7 correlated with remodeled arterioles rats. Moreover, levels significantly increased by induction CXCL12, indicating CXCL12-CXCR7 axis participates PAH. During hypoxia-PAH, inhibition reduces right ventricular systolic pressure (RVSP), Fulton index, arteriosclerosis remodeling. Further study indicated reduced downregulating MMP2, via p38 MAPK pathway. It additionally stimulated phosphorylation pathway, which contributing factor decrease MMP2 following preconditioning SB203580, inhibited MAPK. Conclusions: summary, these findings suggest plays critical PAH, therapy can be developed further targeting its potential targets.