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LncRNA Gm16023通过通过miR-377-3p/Sirt1轴调节巨细胞极化来改善高血糖症加重的败血性肠损伤

Fang Tan¹, Lei Zheng², Dongdong Yuan³

¹Department of Anesthesiology, the Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen 518107, China; Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou 510060, China.

Molecular therapy : the journal of the American Society of Gene Therapy

|March 1, 2026

概括

高血糖症通过促进巨细胞活动,增加了败血症和肠道损伤的风险. 一种针对Gm16023/miR-377-3p/Sirt1通路的新型RNA疗法显示出治疗糖尿病败血症的前景.

科学领域:

内分泌学在内分泌学.
免疫学免疫学免疫学
分子生物学分子生物学

背景情况:

糖尿病与炎症和败血症有关,但机制尚不清楚.
高血糖是糖尿病的关键因素,可能会恶化败血症的结果.
了解糖尿病败血症的分子基础对于开发有效的治疗方法至关重要.

研究的目的:

为了调查高血糖和败血症风险之间的关联.
阐明巨细胞和特定分子通路在高血糖症恶化性败血症中的作用.
开发和测试一种基于RNA的糖尿病败血症治疗策略.

主要方法:

对英国生物库数据 (n=404,184) 的流行病学分析,以评估高血糖和败血症风险.
使用小鼠模型和细胞培养的体内和体外研究来检查巨细胞透和肠道炎症.
基因 (CD11b-DTR) 和化学 (clodronate脂质体) 巨细胞耗尽模型.
RNA测序以确定调节途径,重点关注长非编码RNA (lncRNAs).
基于脂质纳米粒子 (LNP) 的治疗RNA (lncRNA Gm16023) 传递系统的开发.

主要成果:

高血糖明显与大量人类队列中败血症风险增加相关.
过高血糖症加剧了肠道炎症和巨细胞透在败血症条件下.
巨细胞枯竭改善了高血糖引起的败血症肠道损伤.
确定了lncRNA Gm16023的低表达,作为miR-377-3p的竞争性内源RNA (ceRNA),从而调节Sirt1表达和M1巨细胞两极分化.
用LNP封装的Gm16023等离子体系统在体内表现出高效的输送和对肠道损伤的保护作用.

结论:

高血糖症通过lncRNA Gm16023/miR-377-3p/Sirt1轴促进巨驱动的败血性肠损伤.
巨细胞在高血糖症相关的败血症中起着关键的病原性作用.
这项研究强调了一种潜在的基于RNA的治疗方法,用于治疗糖尿病败血症.

相关概念视频

MicroRNAs

MicroRNAs

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...