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miR-141-5p/ZNF705A对慢性粒细胞白血病细胞源外泌体调控骨髓间充质干细胞黏附作用的机制

中国药理学通报 2024年第3期40卷 506-514页

作者：鲍静许晗汪万杰许婷婷戴霁菲夏瑞祥安徽医科大学第一附属医院血液科安徽合肥230032

目的探讨慢性粒细胞白血病(chronic myeloid leukemia,CML)细胞源外泌体(exosome,Exo)中miR-141-5p/ZNF705A对骨髓间充质干细胞(bone marrow mesenchymal stem cells,BMSCs)黏附作用的影响。方法电镜和NTA粒径分析检测CML患者外周血和K562细胞中的Exo形态大小;qRT-pCR和Western blot检测转染前后K562细胞的Exo、BMSCs标记分子及黏附蛋白的表达情况;细胞黏附实验检测BMSCs的黏附能力;CCK-8法检测BMSCs活性、萤光素酶实验检测miR-141-5p与ZNF705A结合情况等。结果qRT-pCR结果显示,miR-141-5p表达在CML患者和K562细胞源Exo中均明显降低;qRT-pCR和Western blot等结果表明,CML患者中BMSCs的黏附蛋白CD44和CXCL12表达明显降低,且能够吞噬K562细胞源Exo。进一步发现,与CD34^(+)细胞相比,K562源性Exo能够降低Exo促进的BMSCs中CD44和CXCL12表达和黏附作用;同时,双萤光素酶基因报告等验证miR-141-5p与ZNF705A靶向结合;最后发现通过上调K562细胞源Exo中miR-141-5p的表达,靶向抑制ZNF705A,进而促进BMSCs的活性和黏附功能。结论K562细胞下调Exo中miR-141-5p表达,减少对ZNF705A的靶向抑制,进而抑制BMSCs的黏附功能,从而调控CML患者的骨髓造血功能。

关键词： mirna-141-5p K562细胞骨髓间充质干细胞 ZNF705A 外泌体慢性粒细胞白血病

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mirna-141-5p Affects the Levels of Neutrophil Elastase in preeclampsia by Regulating MApK1

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Maternal-Fetal Medicine 2022年第4期4卷 238-244页

作者： Keyan Cheng Jialei Cui Wenli Zhou Huiqiang Liu Taotao Yang Yonghong Wang Department of Gynecology and Obstetrics The Second Hospital of Shanxi Medical UniversityTaiyuan 030001China.

Objective:The objective of this study was to investigate the expression levels of microRNA-141-5p(mirna-141-5p),MApK1 and neutrophil elastase in patients with and without preeclampsia(pE),and the relationship between mirna-141-5p and MApK1 with respect to the secretion of elastase by neutrophils in patients with pE.Methods:Thirty patients with pE and 30 healthy pregnant(Hp)women were recruited from The Second Hospital of Shanxi Medical University,Taiyuan,China,between February 2017 and July 2018.Neutrophils were isolated from 8 mL peripheral blood samples and cultured.We recorded neutrophil count and morphology during culture.Apoptosis was detected by flow cytometry in different groups at 0,24,and 48 h.The expression levels of elastase were detected in neutrophils by enzyme-linked immunosorbent assay,whereas the expression levels of mirna-141-5p in peripheral blood neutrophils were detected by real-time polymerase chain reaction.We used TargetScanHuman Release 7.2 to analyze the target genes of mirna-141-5p.The expression of MApK1 in peripheral blood neutrophils was detected by western blotting.Data were analyzed by SpSS version 21.0 software,and comparisons between groups were carried out with the Studentt test.Results:There was no significant difference between the pE and Hp groups(p>0.050)with regard to age or body mass index.The weight of newborns in the pE group(2846.00±600.00 g)was significantly lower than that in the Hp group(3055.00±230.68 g).The number of neutrophilic granulocytes(NGs)in blood samples from the pE group was significantly higher than that in the Hp group(p=0.003).There was no significant difference between the groups with regard to morphology.Apoptosis in the pE group was delayed when compared with the Hp group at different time points.Thep value of apoptosis in the pE and Hp groups were respectively 0.790,pression levels of mirna-141-5p in the pE group were significantly lower than those in the Hp group(p50).The expression levels of MApK1 in

关键词： preeclampsia Neutrophil mirna-141-5p MApK1 Neutrophil elastase

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