Department of Neurosurgery, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, No. 32, West Section 2, 1st Ring Road, Chengdu, 610072, Sichuan Province, People's Republic of China.
Department of Neurosurgery Intensive Care Unit, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, No. 32, West Section 2, 1st Ring Road, Chengdu, 610072, Sichuan Province, People's Republic of China.
Cell Biol Toxicol. 2022 Aug;38(4):649-665. doi: 10.1007/s10565-021-09652-7. Epub 2022 Jan 3.
Our current study is conducted with intention to explore the regulatory mechanism of mesenchymal stem cell (MSC)-derived extracellular vesicle (EV)-miR-744-5p in glioma.
Expression patterns of TGFB1, TGFBR1, and miR-744-5p were determined. EVs were isolated from human MSCs, which were characterized. Then, macrophages were co-cultured with MSCs with ectopic miR-744-5p expression to explore its role in cell proliferation, invasion, and migration capabilities. A nude mouse model of glioma xenograft was developed to observe the tumorigenesis and metastasis ability of glioma in vivo.
TGFB1 and TGFBR1 were upregulated in glioma. TGFB1 promoted M2 polarization of macrophages through theMAPK signaling, thereby promoting the progression of glioma. MSC-EVs suppressed TGFB1 expression in macrophages and inhibited M2 polarization of macrophages. MSC-EVs-miR-744-5p/TGFB1/MAPK axis inhibited M2 polarization of macrophages and reduced the malignant phenotypes of glioma cells. In vivo experiments verified that MSC-EVs-miR-744-5p inhibited the polarization of macrophage M2 and prevented glioma progression.
Taken together, MSC-EVs-miR-744-5p may suppress the MAPK signaling activity by downregulating TGFB1, and then inhibit polarization of macrophages M2, thereby preventing the progression of glioma. Graphical Headlights 1. TGFB1 promotes the M2 polarization of macrophages via the MAPK signaling. 2. miR-744-5p carried by MSC-EVs targets and inhibits TGFB1. 3. MSC-EV-miR-744-5p inhibits M2 polarization of macrophages to prevent glioma progression. 4. miR-744-5p loaded by MSC-EVs may be a preventive strategy against glioma.
本研究旨在探讨间充质干细胞（MSC）衍生的细胞外囊泡（EV）-miR-744-5p 对胶质瘤的调控机制。
检测 TGFB1、TGFBR1 和 miR-744-5p 的表达模式。从人 MSC 中分离 EV，并对其进行特征鉴定。然后，将表达外源性 miR-744-5p 的 MSC 与巨噬细胞共培养，以探讨其对细胞增殖、侵袭和迁移能力的影响。建立胶质瘤异种移植裸鼠模型，观察体内胶质瘤的致瘤和转移能力。
TGFB1 和 TGFBR1 在胶质瘤中上调。TGFB1 通过 MAPK 信号促进巨噬细胞 M2 极化，从而促进胶质瘤的进展。MSC-EVs 抑制巨噬细胞中 TGFB1 的表达，并抑制巨噬细胞 M2 极化。MSC-EVs-miR-744-5p/TGFB1/MAPK 轴抑制巨噬细胞 M2 极化，降低胶质瘤细胞的恶性表型。体内实验证实，MSC-EVs-miR-744-5p 抑制巨噬细胞 M2 极化，阻止胶质瘤进展。
综上所述，MSC-EVs-miR-744-5p 可能通过下调 TGFB1 抑制 MAPK 信号活性，进而抑制巨噬细胞 M2 极化，从而阻止胶质瘤的进展。
