交联CD44通过Fas途径促进人肥大细胞白血病HMC-1细胞的凋亡
发布时间：2019-02-24 16:12
【摘要】：目的:探讨交联CD44分子对人肥大细胞白血病HMC-1细胞株Fas表达及其介导的细胞凋亡的影响。方法:应用流式细胞术检测HMC-1细胞表面CD44及Fas的表达,并观察透明质酸(native hyaluronan,HA)、低分子质量透明质酸(fragmented hyaluronan,F-HA)处理或抗体交联CD44分子后细胞表面Fas表达的变化,进而检测PI3K、PKC及MAPK信号通路抑制剂、蛋白质合成抑制剂和肌动蛋白聚合抑制剂对CD44分子交联后细胞表面Fas表达的影响,用Northern杂交技术检测交联CD44对Fas mRNA表达的影响,用Annexin V/PI双染法检测交联CD44、HA或F-HA对Fas介导的细胞凋亡的影响。结果:HMC-1细胞高表达CD44而低表达Fas,交联CD44分子显著上调细胞表面Fas的表达(P0.05),而Fas mRNA转录水平没有明显变化;肌动蛋白聚合抑制剂细胞松弛素B能抑制CD44上调的Fas表达(P0.05),所检测细胞信号通路抑制剂和蛋白质合成抑制剂均未能抑制Fas表达的上调(P0.05);F-HA和交联CD44均能够促进Fas介导的细胞凋亡(P0.05)。结论:CD44分子可上调HMC-1细胞的Fas表达并放大Fas介导的细胞凋亡,CD44分子可能成为肥大细胞白血病治疗的新靶点。
[Abstract]:Aim: to investigate the effect of cross-linked CD44 on Fas expression and apoptosis in HMC-1 cells of human mast cell leukemia. Methods: flow cytometry was used to detect the expression of CD44 and Fas on the surface of HMC-1 cells, and to observe the expression of native hyaluronan,HA and (fragmented hyaluronan, of low molecular weight hyaluronic acid. The changes of Fas expression on cell surface were detected after F-HA treatment or antibody crosslinking CD44 molecule, and then PI3K,PKC and MAPK signal pathway inhibitors were detected. The effects of protein synthesis inhibitor and actin polymerization inhibitor on the expression of Fas on the cell surface after CD44 molecular crosslinking were studied. The effect of cross-linked CD44 on Fas mRNA expression was detected by Northern hybridization, and cross-linked CD44, was detected by Annexin V/PI double staining. Effect of HA or F-HA on apoptosis mediated by Fas. Results: high expression of CD44 and low expression of Fas, crosslinked CD44 in HMC-1 cells significantly up-regulated the expression of Fas on the cell surface (P0.05), while the level of Fas mRNA transcription did not change significantly. Actin polymerization inhibitor cytochalasin B could inhibit the up-regulated Fas expression of CD44 (P0.05). Neither the signal pathway inhibitor nor protein synthesis inhibitor could inhibit the up-regulation of Fas expression (P0.05). Both F-HA and CD44 could promote apoptosis mediated by Fas (P0.05). Conclusion: CD44 can up-regulate the expression of Fas in HMC-1 cells and amplify the apoptosis mediated by Fas. CD44 may be a new target for the treatment of mast cell leukemia.
【作者单位】： 河北医科大学第四医院肿瘤研究所免疫室;河北医科大学第四医院科研中心;产业医科大学附属病院第一内科;
【基金】：国家自然科学基金资助项目(No.81402228) 河北省自然科学基金资助项目(No.H2015206216) 河北省医学基金资助项目(No.ZL20140334) 河北省教育基金资助项目(No.QN2014049)~~
【分类号】：R733.7
[Abstract]:Aim: to investigate the effect of cross-linked CD44 on Fas expression and apoptosis in HMC-1 cells of human mast cell leukemia. Methods: flow cytometry was used to detect the expression of CD44 and Fas on the surface of HMC-1 cells, and to observe the expression of native hyaluronan,HA and (fragmented hyaluronan, of low molecular weight hyaluronic acid. The changes of Fas expression on cell surface were detected after F-HA treatment or antibody crosslinking CD44 molecule, and then PI3K,PKC and MAPK signal pathway inhibitors were detected. The effects of protein synthesis inhibitor and actin polymerization inhibitor on the expression of Fas on the cell surface after CD44 molecular crosslinking were studied. The effect of cross-linked CD44 on Fas mRNA expression was detected by Northern hybridization, and cross-linked CD44, was detected by Annexin V/PI double staining. Effect of HA or F-HA on apoptosis mediated by Fas. Results: high expression of CD44 and low expression of Fas, crosslinked CD44 in HMC-1 cells significantly up-regulated the expression of Fas on the cell surface (P0.05), while the level of Fas mRNA transcription did not change significantly. Actin polymerization inhibitor cytochalasin B could inhibit the up-regulated Fas expression of CD44 (P0.05). Neither the signal pathway inhibitor nor protein synthesis inhibitor could inhibit the up-regulation of Fas expression (P0.05). Both F-HA and CD44 could promote apoptosis mediated by Fas (P0.05). Conclusion: CD44 can up-regulate the expression of Fas in HMC-1 cells and amplify the apoptosis mediated by Fas. CD44 may be a new target for the treatment of mast cell leukemia.
【作者单位】： 河北医科大学第四医院肿瘤研究所免疫室;河北医科大学第四医院科研中心;产业医科大学附属病院第一内科;
【基金】：国家自然科学基金资助项目(No.81402228) 河北省自然科学基金资助项目(No.H2015206216) 河北省医学基金资助项目(No.ZL20140334) 河北省教育基金资助项目(No.QN2014049)~~
【分类号】：R733.7
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