Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China.
Department of Surgery, UT Southwestern Medical Center, Dallas, TX, 75390, USA.
Biol Direct. 2024 Nov 18;19(1):117. doi: 10.1186/s13062-024-00568-w.
Sepsis is a severe condition characterized by multiple organ dysfunction resulting from an imbalanced host immune response to infections. miRNAs play a crucial role in regulating various biological processes. However, the precise role of miR-31 in the immunopathology of sepsis remains poorly understood.
The concentration of hsa-miR-31-5p in patients with sepsis (both survivors and non-survivors) and healthy individuals was assayed. Using an experimental sepsis model of caecal ligation and puncture (CLP), the impact of mmu-miR-31-5p on survival, organ injury, and inflammation was evaluated. Additionally, the effect of mmu-miR-31-5p on macrophage polarization through Chi3l1 was investigated. Lastly, the therapeutic effects of miPEP31 on experimental sepsis were examined.
The results of miRNA sequencing (miRNA-seq) and quantitative polymerase chain reaction (q-PCR) analyses identified hsa-miR-31-5p as a potential biomarker for patients with sepsis, with non-survivors showing higher levels of hsa-miR-31-5p in peripheral blood mononuclear cells (PBMCs) compared to survivors. Functional studies conducted on peritoneal elucidated macrophages (PEMs) demonstrated that mmu-miR-31-5p inhibits M2 polarization in macrophages by downregulating Chi3l1. The utilization of miPEP31 as a therapeutic intervention had a substantial impact on reducing mortality rates, mitigating organ damage, inducing macrophage polarization towards the M2 phenotype, and suppressing the inflammatory response in murine models of severe sepsis.
The suppression of miR-31 in sepsis plays a protective role in the host defense response by upregulating Chi3l1, highlighting the potential therapeutic efficacy of miPEP31 in sepsis treatment.
脓毒症是一种严重的疾病，其特征是宿主对感染的免疫反应失衡导致多器官功能障碍。miRNAs 在调节各种生物学过程中起着至关重要的作用。然而，miR-31 在脓毒症的免疫病理学中的确切作用仍知之甚少。
检测脓毒症患者（包括幸存者和非幸存者）和健康个体中 hsa-miR-31-5p 的浓度。使用盲肠结扎和穿刺（CLP）实验性脓毒症模型，评估 mmu-miR-31-5p 对存活率、器官损伤和炎症的影响。此外，还研究了 mmu-miR-31-5p 通过 Chi3l1 对巨噬细胞极化的影响。最后，检查了 miPEP31 对实验性脓毒症的治疗效果。
miRNA 测序（miRNA-seq）和定量聚合酶链反应（q-PCR）分析的结果确定 hsa-miR-31-5p 是脓毒症患者的潜在生物标志物，与幸存者相比，非幸存者外周血单核细胞（PBMCs）中的 hsa-miR-31-5p 水平更高。在腹膜阐明巨噬细胞（PEMs）上进行的功能研究表明，mmu-miR-31-5p 通过下调 Chi3l1 抑制巨噬细胞的 M2 极化。miPEP31 作为一种治疗干预的应用对降低死亡率、减轻器官损伤、诱导巨噬细胞向 M2 表型极化以及抑制严重脓毒症小鼠模型中的炎症反应有显著影响。
脓毒症中 miR-31 的抑制通过上调 Chi3l1 对宿主防御反应起着保护作用，突出了 miPEP31 在脓毒症治疗中的潜在治疗效果。
