BACKGROUND Carotid atherosclerosis is a complex disease involving multiple cellular and molecular pathways.Mesenchymal stem cells(MSCs)show therapeutic potential,but their optimal targets and efficacy are still under ...BACKGROUND Carotid atherosclerosis is a complex disease involving multiple cellular and molecular pathways.Mesenchymal stem cells(MSCs)show therapeutic potential,but their optimal targets and efficacy are still under study.MiR-126 enhances endothelial function and promotes angiogenesis by relieving vascular endothelial growth factor signaling suppression,suggesting its potential in vascular rege-neration.However,its role in directing stem cell differentiation toward endo-thelial lineages remains unclear.We hypothesize that miR-126 may influence MSCs’immunomodulatory and vascular reparative functions via the mitogen-activated protein kinases/extracellular signal-regulated kinase(MAPK/ERK)pathway,thereby improving carotid atherosclerosis.This study explores this mechanism to provide novel insights and support the development of miR-126-based therapeutic strategies.AIM To verify if miR-126 inhibits carotid atherosclerosis via the MAPK/ERK pathway.METHODS Rat bone marrow MSCs(product No.CP-R131,Wuhan,China)were verified by flow cytometry.The effects of miR-126 on MSCs’proliferation,migration,apoptosis,and cytokine expression were explored using microRNA mimics and inhibitors.Fluorescence staining quantified CD31+cells to evaluate endothelial differentiation.In vivo differentiation was assessed,and MSCs were transplanted into a rat carotid artery balloon dilatation model.Rats were randomly divided into five groups:Control,negative control mimics,miR-126 mimics,negative control inhibitor,and miR-126 inhibitor.RESULTS In vitro,MSCs treated with miR-126 mimics demonstrated enhanced proliferation,increased migration,and reduced apoptosis.These miR-126 mimics also significantly increased the secretion of vascular endothelial growth factor and basic fibroblast growth factor.Fluorescence and tissue staining indicated a higher proportion of CD31+cells in the miR-126 mimics group.Additionally,the expression of endothelial-related genes(von Willebrand factor,endothelial nitric oxide synthase,and vascular endothelial-cadherin)was upregulated in this group.In vivo,miR-126-transfected MSCs effectively reduced neointimal thickness and promoted endothelial coverage in rats.MiR-126 stimulated MSC proliferation in a dose-dependent manner and reduced p38 and ERK1/2 phosphorylation.Conversely,miR-126 inhibition or blank controls resulted in opposing effects.CONCLUSION MiR-126 exerts significant modulatory effects on the immunoregulatory and vascular reparative functions of MSCs through the MAPK/ERK signaling pathway,promoting their differentiation into endothelial cells and thereby mitigating atherosclerosis.展开更多
目的进一步探讨缺氧后血管新生的调控机制。方法常规方法培养人微血管内皮细胞,低氧培养箱制备内皮细胞缺氧模型(观察组),正常细胞作为对照组。采用real time PCR法检测两组内皮特异性microRNA(miR-210、miR-92a、miR-126)表达变化。结...目的进一步探讨缺氧后血管新生的调控机制。方法常规方法培养人微血管内皮细胞,低氧培养箱制备内皮细胞缺氧模型(观察组),正常细胞作为对照组。采用real time PCR法检测两组内皮特异性microRNA(miR-210、miR-92a、miR-126)表达变化。结果与对照组比较,miR-210、miR-92a、miR-126分别上调了(5.19±0.99)、(3.02±0.88)、(3.87±0.83)倍,P均<0.05。结论缺氧可促使内皮细胞特异性microRNA表达改变,此可能为缺氧后血管新生的主要调控机制。展开更多
基金Supported by Hangzhou Bio-Medicine and Health Industry Development Support Science and Technology Project,No.2022WJC005,No.2024WJC105.
文摘BACKGROUND Carotid atherosclerosis is a complex disease involving multiple cellular and molecular pathways.Mesenchymal stem cells(MSCs)show therapeutic potential,but their optimal targets and efficacy are still under study.MiR-126 enhances endothelial function and promotes angiogenesis by relieving vascular endothelial growth factor signaling suppression,suggesting its potential in vascular rege-neration.However,its role in directing stem cell differentiation toward endo-thelial lineages remains unclear.We hypothesize that miR-126 may influence MSCs’immunomodulatory and vascular reparative functions via the mitogen-activated protein kinases/extracellular signal-regulated kinase(MAPK/ERK)pathway,thereby improving carotid atherosclerosis.This study explores this mechanism to provide novel insights and support the development of miR-126-based therapeutic strategies.AIM To verify if miR-126 inhibits carotid atherosclerosis via the MAPK/ERK pathway.METHODS Rat bone marrow MSCs(product No.CP-R131,Wuhan,China)were verified by flow cytometry.The effects of miR-126 on MSCs’proliferation,migration,apoptosis,and cytokine expression were explored using microRNA mimics and inhibitors.Fluorescence staining quantified CD31+cells to evaluate endothelial differentiation.In vivo differentiation was assessed,and MSCs were transplanted into a rat carotid artery balloon dilatation model.Rats were randomly divided into five groups:Control,negative control mimics,miR-126 mimics,negative control inhibitor,and miR-126 inhibitor.RESULTS In vitro,MSCs treated with miR-126 mimics demonstrated enhanced proliferation,increased migration,and reduced apoptosis.These miR-126 mimics also significantly increased the secretion of vascular endothelial growth factor and basic fibroblast growth factor.Fluorescence and tissue staining indicated a higher proportion of CD31+cells in the miR-126 mimics group.Additionally,the expression of endothelial-related genes(von Willebrand factor,endothelial nitric oxide synthase,and vascular endothelial-cadherin)was upregulated in this group.In vivo,miR-126-transfected MSCs effectively reduced neointimal thickness and promoted endothelial coverage in rats.MiR-126 stimulated MSC proliferation in a dose-dependent manner and reduced p38 and ERK1/2 phosphorylation.Conversely,miR-126 inhibition or blank controls resulted in opposing effects.CONCLUSION MiR-126 exerts significant modulatory effects on the immunoregulatory and vascular reparative functions of MSCs through the MAPK/ERK signaling pathway,promoting their differentiation into endothelial cells and thereby mitigating atherosclerosis.
文摘目的进一步探讨缺氧后血管新生的调控机制。方法常规方法培养人微血管内皮细胞,低氧培养箱制备内皮细胞缺氧模型(观察组),正常细胞作为对照组。采用real time PCR法检测两组内皮特异性microRNA(miR-210、miR-92a、miR-126)表达变化。结果与对照组比较,miR-210、miR-92a、miR-126分别上调了(5.19±0.99)、(3.02±0.88)、(3.87±0.83)倍,P均<0.05。结论缺氧可促使内皮细胞特异性microRNA表达改变,此可能为缺氧后血管新生的主要调控机制。
