TROY(TNFRSF expressed on the mouse embryo)是近年新发现的表达于小鼠胚胎的肿瘤坏死因子受体超家族成员。TROY在体内分布广泛,尤其高表达于胚胎和成熟的中枢神经系统。研究表明,TROY能与髓鞘抑制因子Nogo NgR1及脑内神经再生抑制因子...TROY(TNFRSF expressed on the mouse embryo)是近年新发现的表达于小鼠胚胎的肿瘤坏死因子受体超家族成员。TROY在体内分布广泛,尤其高表达于胚胎和成熟的中枢神经系统。研究表明,TROY能与髓鞘抑制因子Nogo NgR1及脑内神经再生抑制因子(LINGO-1)形成功能受体复合物,参与中枢神经系统轴突生长抑制因子的信号转导;TROY还能诱导细胞副凋亡,促进某些细胞的增殖分化。本文就TROY在上述相关领域的研究进展作一综述。展开更多
目的:S100钙结合蛋白A9(S100A9)激活核因子κB(NF-κB)促进小胶质细胞toll样受体7(TLR7)的表达和炎症因子释放的作用及其机制研究。方法:CCK-8实验检测BV2小胶质细胞的增殖率;转录组测序并结合GO分析、KEGG富集分析和STRING数据库对差...目的:S100钙结合蛋白A9(S100A9)激活核因子κB(NF-κB)促进小胶质细胞toll样受体7(TLR7)的表达和炎症因子释放的作用及其机制研究。方法:CCK-8实验检测BV2小胶质细胞的增殖率;转录组测序并结合GO分析、KEGG富集分析和STRING数据库对差异基因(DEGs)进行比对并从差异表达基因中筛选出目标基因;Real time RT-PCR验证TLR7的表达;免疫荧光染色检测CD68、CD206的表达;Western Blot检测CD68、CD206、TLR7、p65、p-p65的表达;ELISA检测白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)的表达。结果:中等浓度的S100A9对小胶质细胞无增殖抑制效应;实验组CD68蛋白的表达水平较对照组明显增加,而CD206蛋白的表达水平明显下降,提示S100A9促进BV2小胶质细胞向促炎型激活;Toll样受体4(TLR4)的抑制剂TAK-242明显抑制S100A9刺激BV2小胶质细胞后TNF-α和IL-6的表达水平;TLR4/NF-κB通路激活促进TLR7蛋白表达。结论:中等浓度的S100A9可以促进小胶质细胞向促炎型极化,通过激活TLR4/NF-κB通路促进TLR7表达和包括TNF-α和IL-6在内的多种炎症因子的释放,S100A9具有明显的促炎作用。展开更多
Potassium-calcium activates channel subfamily N member 3(KCNN3/SK3/KCa2.3)is involved in regulating cellular calcium signaling,muscle contraction and neurotransmitter release.Dysregulation of the KCNN3 channel is asso...Potassium-calcium activates channel subfamily N member 3(KCNN3/SK3/KCa2.3)is involved in regulating cellular calcium signaling,muscle contraction and neurotransmitter release.Dysregulation of the KCNN3 channel is associated with the development of various tumors.We use bioinformatics analysis to identify whether KCNN3 regulates the occurrence and development of stomach adenocarcinoma(STAD)as a prognostic target.By analyzing the Human Protein Atlas(HPA)database and The Cancer Genome Atlas(TCGA)database,we found that the protein and mRNA levels of KCNN3 were dramatically reduced in STAD,and TCGA database showed that KCNN3 significantly correlated with the prognosis and clinical features of STAD.In addition,we found that high expression of KCNN3 in STAD reduced the IC 50 of several drugs in STAD cells,suggesting that high expression of KCNN3 correlated with the drug sensitivity of STAD.To investigate the underlying biological mechanism,we identified a potential KCNN3 interaction factor,tumor necrosis factor receptor superfamily member 7(CD27/TNFRSF7),which is expressed at low levels in STAD.RT-qPCR and Western blotting confirmed that KCNN3 and CD27 positively correlated with each other at protein and mRNA levels,and co-immunoprecipitation and immunofluorescence experiments confirmed that the two proteins interact and colocalize in the cytoplasm.Moreover,we confirmed the inhibitory effect of KCNN3 on the proliferation,migration and invasion of human STAD cells in vitro and in vivo through subcutaneous tumorigenesis and cellular experiments.Furthermore,GO/KEGG enrichment analysis showed that KCNN3 was enriched in signaling pathways regulating the immune response and calcium or metal ion transport.Lastly,we verified through cell co-culture,RT-qPCR and CCK8 assays that high expression of KCNN3 can promote the increase of T cell activating factor and the killing effect of T cells on STAD cells.Therefore,our results suggest that KCNN3 is a potential inhibitory factor affecting the occurrence and progression of STAD.展开更多
文摘TROY(TNFRSF expressed on the mouse embryo)是近年新发现的表达于小鼠胚胎的肿瘤坏死因子受体超家族成员。TROY在体内分布广泛,尤其高表达于胚胎和成熟的中枢神经系统。研究表明,TROY能与髓鞘抑制因子Nogo NgR1及脑内神经再生抑制因子(LINGO-1)形成功能受体复合物,参与中枢神经系统轴突生长抑制因子的信号转导;TROY还能诱导细胞副凋亡,促进某些细胞的增殖分化。本文就TROY在上述相关领域的研究进展作一综述。
文摘目的:S100钙结合蛋白A9(S100A9)激活核因子κB(NF-κB)促进小胶质细胞toll样受体7(TLR7)的表达和炎症因子释放的作用及其机制研究。方法:CCK-8实验检测BV2小胶质细胞的增殖率;转录组测序并结合GO分析、KEGG富集分析和STRING数据库对差异基因(DEGs)进行比对并从差异表达基因中筛选出目标基因;Real time RT-PCR验证TLR7的表达;免疫荧光染色检测CD68、CD206的表达;Western Blot检测CD68、CD206、TLR7、p65、p-p65的表达;ELISA检测白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)的表达。结果:中等浓度的S100A9对小胶质细胞无增殖抑制效应;实验组CD68蛋白的表达水平较对照组明显增加,而CD206蛋白的表达水平明显下降,提示S100A9促进BV2小胶质细胞向促炎型激活;Toll样受体4(TLR4)的抑制剂TAK-242明显抑制S100A9刺激BV2小胶质细胞后TNF-α和IL-6的表达水平;TLR4/NF-κB通路激活促进TLR7蛋白表达。结论:中等浓度的S100A9可以促进小胶质细胞向促炎型极化,通过激活TLR4/NF-κB通路促进TLR7表达和包括TNF-α和IL-6在内的多种炎症因子的释放,S100A9具有明显的促炎作用。
文摘Potassium-calcium activates channel subfamily N member 3(KCNN3/SK3/KCa2.3)is involved in regulating cellular calcium signaling,muscle contraction and neurotransmitter release.Dysregulation of the KCNN3 channel is associated with the development of various tumors.We use bioinformatics analysis to identify whether KCNN3 regulates the occurrence and development of stomach adenocarcinoma(STAD)as a prognostic target.By analyzing the Human Protein Atlas(HPA)database and The Cancer Genome Atlas(TCGA)database,we found that the protein and mRNA levels of KCNN3 were dramatically reduced in STAD,and TCGA database showed that KCNN3 significantly correlated with the prognosis and clinical features of STAD.In addition,we found that high expression of KCNN3 in STAD reduced the IC 50 of several drugs in STAD cells,suggesting that high expression of KCNN3 correlated with the drug sensitivity of STAD.To investigate the underlying biological mechanism,we identified a potential KCNN3 interaction factor,tumor necrosis factor receptor superfamily member 7(CD27/TNFRSF7),which is expressed at low levels in STAD.RT-qPCR and Western blotting confirmed that KCNN3 and CD27 positively correlated with each other at protein and mRNA levels,and co-immunoprecipitation and immunofluorescence experiments confirmed that the two proteins interact and colocalize in the cytoplasm.Moreover,we confirmed the inhibitory effect of KCNN3 on the proliferation,migration and invasion of human STAD cells in vitro and in vivo through subcutaneous tumorigenesis and cellular experiments.Furthermore,GO/KEGG enrichment analysis showed that KCNN3 was enriched in signaling pathways regulating the immune response and calcium or metal ion transport.Lastly,we verified through cell co-culture,RT-qPCR and CCK8 assays that high expression of KCNN3 can promote the increase of T cell activating factor and the killing effect of T cells on STAD cells.Therefore,our results suggest that KCNN3 is a potential inhibitory factor affecting the occurrence and progression of STAD.
