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M1巨细胞衍生的外体miR-126-5p通过向拼接因子SRSF11来促进内皮细胞衰老和深静脉血栓症

Peiyu Guo¹, Kaili Du¹, Yu Xiao¹

¹Department of Orthopaedics, The First Affiliated Hospital of Kunming Medical University, Yunnan Province, China.

International immunopharmacology

|December 4, 2025

概括

M1巨细胞外体提供miR-126-5p,抑制SRSF11并促进内皮细胞衰老和深静脉血栓症 (DVT). 这揭示了DVT病变发生过程中的新型外体miRNA拼接因子轴.

科学领域:

血管生物学血管生物学
细胞衰老细胞衰老
血栓形成的分子机制

背景情况:

深静脉血栓症 (DVT) 是一种与内皮功能障碍相关的显著血管并发症.
M1巨分化和外体介导的miRNA输送都与血栓形成有关,但机制尚不清楚.
这项研究研究了M1巨细胞外体中的miR-126-5p及其在内皮衰老和DVT中的作用.

研究的目的:

为了阐明MIR-126-5p在M1巨细胞外体中的调节作用.
确定miR-126-5p及其下游标SRSF11对内皮细胞衰老的影响.
研究这种途径对深静脉血栓形成的贡献.

主要方法:

在体外诱导M0和M1巨细胞,并分离M1外体.
外体体的表征和miR-126-5p的量化.
与HUVECs共同培养外体,以评估衰老和亡.
RIP测试以确认SRSF11与Sirt1/P21前体mRNA结合.
建立小鼠DVT模型,在体内给予miR-126-5p激动剂/对抗剂.

主要成果:

来自M1巨细胞的外体被内皮细胞有效地内化.
miR-126-5p的过度表达促进了内皮细胞衰老和亡;抑制逆转了这些效应.
抑制SRSF11导致Sirt1/P21的增长的亲衰老拼接变体.
在体内,miR-126-5p激动剂加剧了DVT,而激动剂减轻了它,与衰老标志物相关联.

结论:

源自M1巨细胞的外体miR-126-5p抑制SRSF11,失调Sirt1/P21剪接并促进内皮衰老.
这建立了一个新的"外体miRNA-拼接因子-内皮衰老"轴在DVT的发病.
这一途径为DVT干预提供了一个潜在的新目标.

关键词:

另一个替代拼接.深静脉血栓形成的原因是深静脉血栓.内皮细胞是内皮细胞.外基因组是外基因组的组成部分.在SRSF11中,我们可以使用SRSF11.在 miR-126-5p 中使用.

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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...

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...