欧素-1/CCL11通过亲氧化和亲炎症途径促进人类衍生纤维细胞的细胞衰老
Patrícia Lavandoski1, Vinícius Pierdoná1, Rafael Moura Maurmann2
1Programa de Pós-Graduação em Ciências Biológicas, Bioquímica do Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde da Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
Frontiers in immunology
|October 20, 2023
概括
欧素-1 (CCL11) 通过增加氧化应激和DNA损伤,促进肺纤维细胞衰老,导致炎症. 这种化学物质在喘患者中也受到上调,这表明它在喘等与年龄相关的肺部疾病中发挥了作用.
科学领域:
- 肺部医学 肺部医学
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 欧素-1 (CCL11) 是喘中的一个关键化学因子,它参与了欧素细胞向肺部的招募.
- 新兴证据将CCL11与衰老过程联系起来,包括老年人的上调和喘儿童短端粒的相关性.
研究的目的:
- 研究CCL11在促进肺纤维细胞细胞衰老中的作用.
- 在肺衰老的背景下阐明CCL11激活的信号通路.
主要方法:
- 在分析中,使用PseudoCell识别CCL11目标.
- 在人肺纤维细胞 (MRC-5) 中进行了体外验证,这些细胞暴露于复合人CCL11 (rhCCL11).
- 从喘患者的呼吸道上皮细胞中对基因表达的差异分析.
主要成果:
- 在肺纤维细胞中,CCL11诱导反应性氧物种 (ROS) 生产和DNA损伤反应 (DDR) 激活 (p-TP53,γH2AX).
- CCL11促进细胞衰老和炎症性细胞因子 (IL-6,IL-8) 的分泌.
- 喘患者的呼吸道细胞显示CCL11的过度表达与衰老标志物 (CDKN2A,SERPINE1) 一起.
结论:
- CCL11通过ROS和DDR途径促进肺纤维细胞衰老.
- 喘中CCL11升调表明与加速的肺衰老和炎症有联系.
- 向CCL11可能为与年龄相关的肺部疾病,包括喘提供治疗策略.
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