[1]吴西军,刘庆,刘俊峰,等.人脐带间充质干细胞对T细胞活化介导的肺动脉平滑肌细胞增殖抑制及机制研究[J].第三军医大学学报,2019,41(22):2174-2180.
 WU Xijun,LIU Qing,LIU Junfeng,et al.Inhibitory effect and mechanism of human umbilical cordmesenchymal stem cells on T cell activation-mediated proliferation of pulmonary artery smooth muscle cells[J].J Third Mil Med Univ,2019,41(22):2174-2180.
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人脐带间充质干细胞对T细胞活化介导的肺动脉平滑肌细胞增殖抑制及机制研究(/HTML )
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
41卷
期数:
2019年第22期
页码:
2174-2180
栏目:
基础医学
出版日期:
2019-11-30

文章信息/Info

Title:
Inhibitory effect and mechanism of human umbilical cordmesenchymal stem cells on T cell activation-mediated proliferation of pulmonary artery smooth muscle cells
作者:
吴西军刘庆刘俊峰杨小燕何志旭 
贵州医科大学:细胞工程生物医药技术国家地方联合工程实验室,贵州省再生医学重点实验室,中国医学科学院成体干细胞转化研究重点实验室,免疫学教研室,附属医院呼吸内科,附属医院儿童血液肿瘤科
Author(s):
WU Xijun LIU Qing LIU Junfeng YANG Xiaoyan HE Zhixu

National Guizhou Joint Engineering Laboratory for Cell Engineering and Biomedical Technique, Guizhou Provincial Key Laboratory of Regenerative Medicine, Key Laboratory of Adult Stem Cell Translational Research, Department of Immunology, Department of Pediatrics, Affiliated Hospital of Guizhou Medical University, Department of Hematology and Oncology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, 550004, China 

关键词:
间充质干细胞肺动脉平滑肌细胞细胞增殖肿瘤坏死因子&alpha钙调磷酸酶T淋巴细胞核因子
Keywords:
mesenchyma stem cells pulmonary artery smooth muscle cells cell proliferation tumor necrosis factor-&alpha calcineurin T lymphoid nuclear factor
分类号:
R322.121;R329.2;R363.22
文献标志码:
A
摘要:

目的 阐释人脐带间充质干细胞(human umbilical cord mesenchymal stem cells,hu-MSCs)抑制T淋巴细胞活化介导的肺动脉平滑肌细胞(pulmonary artery smooth muscle cells,PASMCs)增殖的作用及可能的调节机制。方法 复苏并培养hu-MSCs和大鼠来源的PASMCs、T细胞,将实验分为PASMCs对照组、T细胞刺激组(PASMCs+T淋巴细胞)、MSC干预组(PASMCs+T淋巴细胞+MSC)、英夫利西单抗干预组(PASMCs+T淋巴细胞+英夫利西单抗)、TNF-α刺激组(PASMCs+T淋巴细胞+MSC+TNF-α)。通过荧光分光光度计、RT-qPCR、倒置荧光显微镜观察等方法研究钙调磷酸酶、T淋巴细胞核因子的变化。结果T淋巴细胞刺激组TNF-α浓度明显升高(P<0.01);MSCs与英夫利西单抗均能明显降低其TNF-α浓度(P<0.01)。与单纯PASMCs对照组比较,T淋巴细胞刺激组PASMCs的增殖能力明显增强(P<0.01),胞浆中游离钙离子的浓度明显升高(P<0.01),胞内CaN的表达(P<0.01)和活性(P<0.01)均显著上调,NFATc2的表达和活性亦显著上调(P<0.01);与T淋巴细胞刺激组相比,MSCs干预组、英夫利西单抗干预组PASMCs的增殖被明显抑制(P<0.01),胞浆中游离钙离子的浓度均明显下降(P<0.01),胞内CaN的表达(P<0.01)和活性(P<0.01)均显著下调,NFATc2的表达(P<0.01)和活性亦下调;外源TNF-α可有效逆转MSC的干预作用,其作用与T淋巴细胞刺激组几乎相当。结论 hu-MSCs可以通过改变CaN、NFATc2的表达和活化状态,抑制T淋巴细胞活化,抑制炎症因子TNF-α导致的PASMCs增殖。

Abstract:
Objective To investigate the inhibitory effect of human umbilical cord mesenchymal stem cells (hu-MSCs) on T lymphocyte activation-mediated proliferation of pulmonary artery smooth muscle cells (PASMCs) and explore the possible regulatory mechanism. MethodsCultured rat PASMCs were stimulated with activated T lymphocytes with subsequent exposures to hu-MSCs, infliximab, or both hu-MSCs and tumor necrosis factor-α (TNF-α). The changes in calcineurin and T lymphoid nuclear factor in the cell cultures were observed using fluorescence spectrophotometer, RT-qPCR and inverted fluorescence microscopy. ResultsAmong all the treatments, stimulation with activated T lymphocytes alone resulted in the highest concentration of TNF-α in the supernatant of PASMC culture (P<0.01). Co-culture with Hu-MSCs and treatment with infliximab both significantly decreased TNF-α concentration in PASMCs stimulated with activated T lymphocytes (P<0.01). Stimulation with T lymphocytes significantly enhanced the proliferative activity of the PASMCs, increased Ca2+ concentration in the cytoplasm, and up-regulated the expression and activity of intracellular CaN and NFATc2. Co-culture with Hu-MSCs and treatment with infliximab significantly suppressed the proliferation of PASMCs stimulated with T lymphocytes, decreased the concentration of Ca2+ in the cytoplasm, and lowered both the expression and activity of intracellular CaN and NFATc2. Exogenous TNF-α obviously reversed the effects of Hu-MSC on the PASMCs, and produced responses similar to T-lymphocyte stimulation in the PASMCs. ConclusionHu-MSCs can promote the proliferation of PASMCs by modulating the expression and activation of CaN and NFATc2 to inhibit the activation of T lymphocytes and the PASMCs proliferation induced by inflammatory factor TNF-α.
 

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更新日期/Last Update: 2019-11-21