MiR-22-3p regulates hypoxia-induced mitochondrial homeostasis and apoptosis of pulmonary artery smooth muscle cells by targeting apoptosis-inducing factor,mitochondrion-associated 1
10.13406/j.cnki.cyxb.003884
- VernacularTitle:miR-22-3p通过靶向AIFM1调控低氧诱导的肺动脉平滑肌细胞线粒体稳态和凋亡
- Author:
Yujing XIANG
1
;
Huting TANG
;
Yong AN
Author Information
1. 重庆医科大学附属儿童医院胸心外科/国家儿童健康与疾病临床医学研究中心/儿童发育疾病研究教育部重点实验室/结构性出生缺陷与器官修复重建重庆市重点实验室,重庆 400010
- Keywords:
pulmonary arterial hypertension;
mitochondrial homeostasis;
apoptosis
- From:
Journal of Chongqing Medical University
2025;50(11):1531-1540
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of miR-22-3p and apoptosis-inducing factor,mitochondrion-associated 1(AIFM1)on mitochondrial homeostasis and apoptosis of pulmonary artery smooth muscle cells(PASMCs)under hypoxic conditions by establishing an in vitro model of pulmonary hypertension(PAH).Methods:PASMCs were cultured under hypoxic conditions to establish an in vitro model of PAH,and the expression levels of AIFM1 and miR-22-3p were upregulated or downregulated.Reverse transcription quantita-tive polymerase chain reaction(RT-qPCR)and Western blotting were used to measure the expression levels of AIFM1,miR-22-3p,and cleaved cysteine-aspartic protease-3(Cleaved Caspase-3).cell counting kit-8(CCK-8)assay was used to measure the prolifera-tive activity of cells,and flow cytometry was used to measure cell apoptosis.Mitochondrial superoxide indicator(mitoSOX)and adenos-ine triphosphate(ATP)assay kits were used to observe mitochondrial function and dynamics,and Mito-Tracker Red CMXRos(Mito-Tracker)was used to measure the change in mitochondrial circum-ference.Dual-luciferase reporter assay was used to validate the interaction between AIFM1 and miR-22-3p.Results:Hypoxia increased the content of mitochondrial ROS,reduced the level of ATP,promoted mitochondrial fission,and reduced cell apoptosis in PASMCs.AIFM1 overexpression improved mitochondrial homeo-stasis and increased cell apoptosis,while miR-22-3p negatively regulated AIFM1 and reversed the effect of AIFM1 overexpression.Conclusion:This study shows that miR-22-3p enhances mitochon-drial homeostasis,proliferation,and apoptosis in hypoxia-induced PASMCs by targeting AIFM1,which provides a potential theoretical basis for the prevention and treatment of PAH.
