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p300/Sp1-Mediated High Expression of p16 Promotes Endothelial Progenitor Cell Senescence Leading to the Occurrence of Chronic Obstructive Pulmonary Disease
Mediators of Inflammation ( IF 4.6 ) Pub Date : 2021-08-20 , DOI: 10.1155/2021/5599364 Zhihui He 1 , Huaihuai Peng 2 , Min Gao 1 , Guibin Liang 2 , Menghao Zeng 1 , Xuefeng Zhang 1
Mediators of Inflammation ( IF 4.6 ) Pub Date : 2021-08-20 , DOI: 10.1155/2021/5599364 Zhihui He 1 , Huaihuai Peng 2 , Min Gao 1 , Guibin Liang 2 , Menghao Zeng 1 , Xuefeng Zhang 1
Affiliation
Objective. Chronic obstructive pulmonary disease (COPD) is a common chronic disease and develops rapidly into a grave public health problem worldwide. However, what exactly causes the occurrence of COPD remains largely unclear. Here, we are trying to explore whether the high expression of p16 mediated by p300/Sp1 can cause chronic obstructive pulmonary disease through promoting the senescence of endothelial progenitor cells (EPCs). Methods. Peripheral blood EPCs were isolated from nonsmoking non-COPD, smoking non-COPD, and smoking COPD patients. The expressions of p16, p300, and senescence-related genes were detected by RT-PCR and Western Blot. Then, we knocked down or overexpressed Sp1 and p300 and used the ChIP assay to detect the histone H4 acetylation level in the promoter region of p16, CCK8 to detect cell proliferation, flow cytometry to detect the cell cycle, and β-galactosidase staining to count the proportion of senescent cells. Results. The high expression of p16 was found in peripheral blood EPCs of COPD patients; the cigarette smoke extract (CSE) led to the increase of p16. The high expression of p16 in EPCs promoted cell cycle arrest and apoptosis. The CSE-mediated high expression of p16 promoted cell senescence. The expression of p300 was increased in peripheral blood EPCs of COPD patients. Moreover, p300/Sp1 enhanced the histone H4 acetylation level in the promoter region of p16, thereby mediating the senescence of EPCs. And knockdown of p300/Sp1 could rescue CSE-mediated cell senescence. Conclusion. p300/Sp1 enhanced the histone H4 acetylation level in the p16 promoter region to mediate the senescence of EPCs.
中文翻译:
p300/Sp1介导的p16高表达促进内皮祖细胞衰老导致慢性阻塞性肺疾病的发生
客观。慢性阻塞性肺疾病(COPD)是一种常见的慢性疾病,并迅速发展成为世界范围内严重的公共卫生问题。然而,究竟是什么原因导致COPD的发生仍不清楚。在这里,我们试图探索p300/Sp1介导的p16的高表达是否可以通过促进内皮祖细胞(EPCs)的衰老而引起慢性阻塞性肺疾病。方法. 从不吸烟的非 COPD、吸烟的非 COPD 和吸烟的 COPD 患者中分离出外周血 EPC。RT-PCR和Western Blot检测p16、p300和衰老相关基因的表达。然后,我们敲低或过表达Sp1和p300并使用ChIP测定法检测p16启动子区的组蛋白H4乙酰化水平,CCK8检测细胞增殖,流式细胞术检测细胞周期,β-半乳糖苷酶染色计数衰老细胞的比例。结果. COPD患者外周血EPCs中发现p16高表达;香烟烟雾提取物(CSE)导致p16的增加。EPCs中p16的高表达促进细胞周期停滞和细胞凋亡。CSE介导的p16高表达促进细胞衰老。COPD患者外周血EPCs中p300表达升高。此外,p300/Sp1 增强了 p16 启动子区域的组蛋白 H4 乙酰化水平,从而介导了 EPCs 的衰老。p300/Sp1 的敲低可以挽救 CSE 介导的细胞衰老。结论。p300/Sp1 增强 p16 启动子区域的组蛋白 H4 乙酰化水平以介导 EPCs 的衰老。
更新日期:2021-08-20
中文翻译:
p300/Sp1介导的p16高表达促进内皮祖细胞衰老导致慢性阻塞性肺疾病的发生
客观。慢性阻塞性肺疾病(COPD)是一种常见的慢性疾病,并迅速发展成为世界范围内严重的公共卫生问题。然而,究竟是什么原因导致COPD的发生仍不清楚。在这里,我们试图探索p300/Sp1介导的p16的高表达是否可以通过促进内皮祖细胞(EPCs)的衰老而引起慢性阻塞性肺疾病。方法. 从不吸烟的非 COPD、吸烟的非 COPD 和吸烟的 COPD 患者中分离出外周血 EPC。RT-PCR和Western Blot检测p16、p300和衰老相关基因的表达。然后,我们敲低或过表达Sp1和p300并使用ChIP测定法检测p16启动子区的组蛋白H4乙酰化水平,CCK8检测细胞增殖,流式细胞术检测细胞周期,β-半乳糖苷酶染色计数衰老细胞的比例。结果. COPD患者外周血EPCs中发现p16高表达;香烟烟雾提取物(CSE)导致p16的增加。EPCs中p16的高表达促进细胞周期停滞和细胞凋亡。CSE介导的p16高表达促进细胞衰老。COPD患者外周血EPCs中p300表达升高。此外,p300/Sp1 增强了 p16 启动子区域的组蛋白 H4 乙酰化水平,从而介导了 EPCs 的衰老。p300/Sp1 的敲低可以挽救 CSE 介导的细胞衰老。结论。p300/Sp1 增强 p16 启动子区域的组蛋白 H4 乙酰化水平以介导 EPCs 的衰老。