CD81 通过阻断 CD274/PD-L1 的选择性自噬降解驱动放射抵抗性胶质母细胞瘤的免疫逃逸
CD81 drives immune evasion in radioresistant glioblastoma by blocking selective autophagic degradation of CD274/PD-L1.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
骨髓间充质干细胞细胞外囊泡来源 miR-27b-3p 通过靶向 SMAD4 激活 Wnt/β-catenin 通路并加重肝脏缺血再灌注损伤
英文原题：Bone Marrow Mesenchymal Stem Cell Extracellular Vesicle-derived miR-27b- 3p activates the Wnt/Β-catenin Pathway by Targeting SMAD4 and Aggravates Hepatic Ischemia-reperfusion Injury.
查看英文原题
Bone Marrow Mesenchymal Stem Cell Extracellular Vesicle-derived miR-27b- 3p activates the Wnt/Β-catenin Pathway by Targeting SMAD4 and Aggravates Hepatic Ischemia-reperfusion Injury.
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研究概要
我们的研究结果揭示了 miR-27 在 HIRI 中的作用及机制，并为 HIRI 的预防和治疗提供了新思路；例如，转染 antimiR-27 的 BMSC 来源 EVs 可能对 HIRI 表现出更好的保护作用。
中文摘要
背景
本研究旨在考察骨髓间充质干细胞（BMSC）分泌的细胞外囊泡（EV）以及 BMSC-EV 中高表达的 miR-27 在肝缺血再灌注损伤（HIRI）中的作用。方法与结果：研究建立 HIRI 小鼠模型，并向腹腔预先注射 agomir-miR-27-3p、agomir-NC、BMSC-EV 或对照 PBS。与 HIRI 组相比，预先注射 BMSC-EV 的 HIRI 小鼠丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）水平显著降低，肝坏死减轻（P < 0.05）。然而，与 HIRI + NC 小鼠相比，HIRI + miR-27b 小鼠 ALT 和 AST 水平显著升高，肝坏死加重，凋亡相关蛋白表达增加（P < 0.05）。缺氧诱导后，转染 miR-27 的 AML-12 细胞，其增殖和凋亡均显著高于 mimic NC 组 AML-12 细胞（P < 0.01）。研究证实 SMAD4 是 miR-27 的靶基因。此外，与 HIRI + NC 小鼠相比，HIRI + miR-27 小鼠 SMAD4 表达显著降低，而 Wnt1、β-catenin、c-Myc 和 Cyclin D1 水平升高。
结论
研究揭示了 miR-27 在 HIRI 中的作用和机制，为 HIRI 的预防与治疗提供了新见解；例如，使用抗 miR-27 转染 BMSC 后来源的 EV，可能对 HIRI 产生更好的保护作用。
展开英文摘要原文
BACKGROUND
To investigate the roles of extracellular vesicles (EVs) secreted from bone marrow mesenchymal stem cells (BMSCs) and miR-27 (highly expressed in BMSC EVs) in hepatic ischemia reperfusion injury (HIRI). APPROACHES AND RESULTS: We constructed a HIRI mouse model and pretreated it with an injection of agomir- miR-27-3p , agomir-NC, BMSC-EVs or control normal PBS into the abdominal cavity. Compared with the HIRI group, HIRI mice preinjected with BMSC-EVs had significantly decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and alleviated liver necrosis (P<0.05). However, compared with HIRI+NC mice, HIRI+ miR-27b mice had significantly increased ALT and AST levels, aggravated liver necrosis, and increased apoptosis-related protein expression (P<0.05). The proliferation and apoptosis of AML-12 cells transfected with miR-27 were significantly higher than the proliferation and apoptosis of AML-12 cells in the mimic NC group (P<0.01) after hypoxia induction. SMAD4 was proven to be a miR-27 target gene. Furthermore, compared to HIRI+NC mice, HIRI+ miR-27 mice displayed extremely reduced SMAD4 expression and increased levels of wnt1, -catenin, c-Myc, and Cyclin D1.
CONCLUSION
Our findings reveal the role and mechanism of miR-27 in HIRI and provide novel insights for the prevention and treatment of HIRI; for example, EVs derived from BMSCs transfected with antimiR- 27 might demonstrate better protection against HIRI.
论文信息
- 作者
- Li H、Lin W、Li Y、Zhang J、Liu R、Qu M、Wang R、Kang X
- 单位
- Department of Public Health, Guilin Medical University, Guilin Guangxi, 541104, China.China
- 期刊
- Current stem cell research & therapy2024
- 原文标识
- PubMed 37680161 · DOI 10.2174/1574888X19666230901140628