关键词: 肺动脉平滑肌细胞, 肺动脉高压, miR-107, 整合素 α2

Abstract: Objective: To investigate the effect of miR-107 and integrin alpha 2 (ITGA2) onpulmonary artery smooth muscle cells ( PASMCs) in pulmonary arterial hypertension ( PAH).Methods Pulmonary artery smooth muscle cells (PASMCs) were cultured under normal and hypoxic conditions. qRT-PCR was applied to detect the expression levels of miR-107 and ITGA2 in the cells. Flow cytometry was used to determine cell cycle and apoptosis. The targeting relationship between miR-107 and ITGA2 was verified by luciferase reporter gene assay. PASMCs were transfected with si-NC and si-miR-107 and cultured under hypoxic conditions, and were divided into the si-NC group and the si-miR-107 group. The expression levels of miR-107 and ITGA2, the cell cycle, and apoptosis were examined. Thirty C57BL / 6 mice were divided into 3 groups: control group, model group, and si-miR-107 treatment group, with the latter two groups injected with si-NC and si-miR- 107 after inducing a PAH model through hypoxia, respectively. The right ventricular hypertrophy in dex (RVHI), right ventricular systolic pressure ( RVSP), and mean pulmonary arterial pressure (mPAP) were measured. The expression levels of miR-107 and ITGA2, and phosphorylated histone H2AX (γH2AX) protein in the mouse lung tissues were detected by qRT-PCR and Western blotting. Results Compared with those of cells in the normal group, the expression level of miR-107 inthe hypoxic group cells was increased, the ITGA2 expression level was decreased, the proportion of cells in the G 1 phase was increased, the proportion of cells in the S phase was decreased, and the apoptosis rate was increased. miR-107 targeted ITGA2. Compared with those in the si-NC group, the expression level of miR-107 in the si-miR-107 group was decreased, the ITGA2 expression level was increased, the proportion of cells in the G1 phase was decreased, the proportion of cells in the S phase was increased, and the apoptosis rate was decreased. In the mice experiments, compared with those in the control group, the values of RVHI, RVSP, and mPAP, the expression level of miR-107 and γH2AX protein was increased, and the ITGA2 expression level was decreased in the model group. Compared with those in the model group, the values of RVHI, RVSP, and mPAP, the expression levels of miR-107 and γH2AX protein were decreased in the si-miR-107 treatmentgroup, while the expression level of ITGA2 was increased. Conclusion miR-107 affects PAH byinhibiting the cell cycle and promoting the apoptosis of PASMCs through ITGA2.

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