血外体miR-17-5p通过向Bcl11b来调节巨细胞极化,用于败血症引起的肺损伤
Ying Xian1,2, Yinfang Sun2, Lifu Wang3
1Department of Respiratory Diseases, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People's Republic of China.
Journal of inflammation research
|August 14, 2025
概括
血外体miR-17-5p在败血症患者中降低,通过向Bcl11b,驱动M1巨分化和肺损伤. 恢复miR-17-5p可能为败血症提供治疗策略.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 败血症是一种危及生命的疾病,涉及炎症和免疫失调,往往导致急性肺损伤.
- 巨细胞的两极分化在败血症中至关重要,但血外体微RNAs (miRNAs),特别是miR-17-5p的作用尚不清楚.
- 转录因子Bcl11b在败血症引起的巨细胞重编程中的作用尚未得到研究.
研究的目的:
- 为了研究血衍生出异位体miR-17-5p在败血症相关的巨细胞极化中的作用.
- 在败血症中确定外体miR-17-5p的分子标和调节机制.
- 探索miR-17-5p-Bcl11b轴作为败血症引起的肺损伤的治疗点的潜力.
主要方法:
- 从败血症患者和对照组的血中分离细胞外囊泡 (EVs).
- 在体外和体内实验中评估外体miR-17-5p对巨细胞极化的影响,使用qRT-PCR,流细胞计,ELISA和西方斑点.
- 转录组测序和双化酶记者测试以阐明miR-17-5p和Bcl11b的调控关系.
主要成果:
- 败血症患者的血外体显示了miR-17-5p的减少,并促进了M1巨细胞两极分化 (增加iNOS,促炎细胞因子).
- miR-17-5p过度表达抑制了M1极化,并减少了巨细胞和小鼠模型中的炎症损伤.
- miR-17-5p直接针对Bcl11b的3'UTR,抑制其表达;Bcl11b的恢复逆转了miR-17-5p的抗炎作用.
结论:
- 血外体miR-17-5p通过向Bcl11b,促进M1巨细胞两极分化和败血症引起的肺损伤.
- 在败血症中发现了一种新的miR-17-5p-Bcl11b调节轴.
- 外体 miR-17-5p 代表了毒症的潜在生物标志物和治疗标.
相关概念视频
01:22MicroRNAs
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
01:01Regulation of Hematopoietic Stem Cells
All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
01:22MicroRNAs
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...