M2 microglial small extracellular vesicles reduce glial scar formation via the miR-124/STAT3 pathway after ischemic stroke in mice.
M2 microglial small extracellular vesicles reduce glial scar formation via the miR-124/STAT3 pathway after ischemic stroke in mice.
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M2小胶质细胞衍生的外泌体通过外泌体miR-124保护小鼠大脑免受缺血再灌注损伤
DOI：
10.7150/thno.48761
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发表时间：
2021
期刊：
影响因子：
12.4
通讯作者：
Zhang Z
中科院分区：
文献类型：
--
作者：
Li Z;Song Y;He T;Wen R;Li Y;Chen T;Huang S;Wang Y;Tang Y;Shen F;Tian HL;Yang GY;Zhang Z
原理：胶质瘢痕是卒中后神经元再生的主要障碍。因此，促进其降解和抑制其形成的方法有利于中风恢复。已知小胶质细胞和星形胶质细胞的相互作用参与中风后的胶质瘢痕形成;然而，小胶质细胞如何影响胶质瘢痕形成仍不清楚。研究方法：在大脑中动脉闭塞后第1天至第7天，每天通过尾静脉注射用M2小胶质细胞小细胞外囊泡处理小鼠。缺血后检测胶质瘢痕、梗死体积、神经功能评分。在缺血后的脑梗死周围区域中检测microRNA和相关蛋白。结果：M2小胶质细胞小细胞外囊泡减少胶质瘢痕形成，促进卒中后恢复，并富含miR-124。此外，M2小胶质细胞小细胞外囊泡处理降低了星形胶质细胞增殖基因信号转导子和转录激活子3（miR-124的靶点之一）和胶质细胞酸性蛋白的表达，并在体外和体内抑制了星形胶质细胞增殖。星形胶质细胞中Notch 1表达降低，Sox 2表达增加，提示星形胶质细胞已转化为神经元祖细胞。最后，M2小胶质细胞小细胞外囊泡中的miR-124敲低阻断了它们对胶质瘢痕和中风恢复的作用。结论：我们的研究结果首次表明，小胶质细胞通过小细胞外囊泡调节胶质瘢痕形成，表明M2小胶质细胞小细胞外囊泡可能代表中风的新治疗方法。
Rationale: Glial scars present a major obstacle for neuronal regeneration after stroke. Thus, approaches to promote their degradation and inhibit their formation are beneficial for stroke recovery. The interaction of microglia and astrocytes is known to be involved in glial scar formation after stroke; however, how microglia affect glial scar formation remains unclear. Methods: Mice were treated daily with M2 microglial small extracellular vesicles through tail intravenous injections from day 1 to day 7 after middle cerebral artery occlusion. Glial scar, infarct volume, neurological score were detected after ischemia. microRNA and related protein were examined in peri-infarct areas of the brain following ischemia. Results: M2 microglial small extracellular vesicles reduced glial scar formation and promoted recovery after stroke and were enriched in miR-124. Furthermore, M2 microglial small extracellular vesicle treatment decreased the expression of the astrocyte proliferation gene signal transducer and activator of transcription 3, one of the targets of miR-124, and glial fibrillary acidic protein and inhibited astrocyte proliferation both in vitro and in vivo. It also decreased Notch 1 expression and increased Sox2 expression in astrocytes, which suggested that astrocytes had transformed into neuronal progenitor cells. Finally, miR-124 knockdown in M2 microglial small extracellular vesicles blocked their effects on glial scars and stroke recovery. Conclusions: Our results showed, for the first time, that microglia regulate glial scar formation via small extracellular vesicles, indicating that M2 microglial small extracellular vesicles could represent a new therapeutic approach for stroke.
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影响因子：
4
作者：
Colombo E;Borgiani B;Verderio C;Furlan R
通讯作者：
Furlan R
影响因子：
25
作者：
Asai H;Ikezu S;Tsunoda S;Medalla M;Luebke J;Haydar T;Wolozin B;Butovsky O;Kügler S;Ikezu T
通讯作者：
Ikezu T
影响因子：
12.4
作者：
Khelif, Yacine;Toutain, Jerome;Bernaudin, Myriam
通讯作者：
Bernaudin, Myriam
DOI：
10.1083/jcb.201709069
发表时间：
2018-02-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hansen DV;Hanson JE;Sheng M
通讯作者：
Sheng M
影响因子：
9.3
作者：
Kumar A;Stoica BA;Loane DJ;Yang M;Abulwerdi G;Khan N;Kumar A;Thom SR;Faden AI
通讯作者：
Faden AI