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国家自然科学基金(81270138)

作品数:3 被引量:12H指数:2
相关作者:耿申吴婷苏欣张晨刘晨阳更多>>
相关机构:南方医科大学南京大学南京医科大学第二附属医院更多>>
发文基金:国家自然科学基金江苏省自然科学基金国家科技支撑计划更多>>
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P38-MK2-HuR通路在急性呼吸窘迫综合征炎症因子表达中的作用被引量:1
2017年
急性呼吸窘迫综合征(ARDS)是常见的临床危重症,是多器官功能障碍最常出现的器官损伤。目前认为ARDS是失控的全身炎症反应导致的非心源性肺水肿,感染、创伤和胰腺炎等多种原因可引起ARDS。其中,感染仍是ARDS最常见的原因。
耿申吴婷周威芮昱雯何骞李红星施毅苏欣
关键词:急性呼吸窘迫综合征非心源性肺水肿通路
Mitogen-activated protein kinase-activated protein kinase 2 regulates tumor necrosis factor-induced interleukin-6 expression via human antigen R被引量:2
2013年
Background Human antigen R (HuR) is a ubiquitously expressed member of the ELAV family, and has relatively high cytoplasmic abundance in lung tissue regenerating after injury. In this study, we investigated whether mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2) and HuR participate in the tumor necrosis factor (TNF)-induced expression of interleukin-6 (IL-6). Methods Human pulmonary microvascular endothelial cells were treated with TNF following short interfering RNAmediated knockdown of MK2 or HuR. Cell supernatants were collected to detect the mRNA and protein expression of IL-6 at different time points, The expression and half-life of IL-6 mRNA were then determined in cells that had been treated with actinomycin D. Finally, after knockdown of MK2, the cytoplasmic expression of HuR protein was analyzed using Western blotting. Results MK2 or HuR knockdown decreased both the mRNA and protein expression of IL-6 in TNF-stimulated cells. In MK2 knockdown cells, the half-life of IL-6 mRNA was reduced to 36 minutes, compared with 67 minutes in the control group. In HuR knockdown cells, the half-life of IL-6 mRNA decreased from 62 minutes to 24 minutes. Further analysis revealed that knockdown of MK2 resulted in reduced HuR protein expression in the cytoplasm. Conclusions MK2 regulates the TNF-induced expression of IL-6 by influencing the cytoplasmic levels of HuR.
XU Jin SU Xin SHI Jia-xin SUN He WU Ting SHI Yi
细胞间黏附分子-1在ARDS小鼠肺微血管内皮细胞内的表达变化被引量:9
2016年
目的细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)在介导中性粒细胞肺部浸润的过程中起到很大作用。在脂多糖(Lipopolysaccharides,LPS)诱导的急性呼吸窘迫综合征小鼠模型中,观察ICAM-1以及丝裂原激活蛋白激酶2(mitogen-activated protein kinase activated protein kinase 2,MK2)和人抗原R(human antigen R,HuR)在小鼠肺微血管内皮细胞(pulmonary microvascular endothelial cell,PMVEC)内表达的变化。方法健康清洁型6~8周雄性C57BL/6小鼠,随机数字表法分为对照组和LPS组,每组5只。LPS组腹腔注射LPS 5 mg/kg(溶于100μL的PBS中),对照组腹腔注射PBS(5mg/kg),24 h处死全部小鼠。在LPS诱导的小鼠ARDS模型中,用Real-time PCR方法检测小鼠肺组织分离得到的PMVEC内人抗原R(human antigen R,HuR)、ICAM-1的mRNA表达量,用Western blot法检测总MK2、磷酸化MK2、HuR以及ICAM-1表达量的变化,利用流式细胞仪检测PMVEC表面ICAM-1的表达量及肺部浸润的中性粒细胞数量。结果 LPS组小鼠肺组织W/D较对照组高,差异有统计学意义[(6.16±0.40)vs(3.61±0.28),P〈0.05]。流式细胞术检测LPS组中性粒细胞浸润率较对照组高[(13.92±3.23)%vs(3.24±1.24)%,P〈0.05]。LPS刺激后小鼠肺组织中ICAM-1的mRNA及蛋白表达较对照组明显增加(P〈0.05),PMVEC表面ICAM-1表达较对照组也明显增加(P〈0.05)。MK2总量无明显变化,磷酸化MK2较对照组明显增加,HuR mRNA及蛋白总量无明显变化,但存在核质转移。结论特异性阻断或减少微血管内皮细胞中HuR的表达可使ICAM-1表达减少,从而减少中性粒细胞的浸润,减轻ARDS病理生理改变,可为临床治疗ARDS提供一个新靶点。
耿申吴婷穆先敏张晨刘晨阳尤强苏欣
关键词:细胞间黏附分子-1
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