Activation of glucagon-like peptide-1 receptor in microglia attenuates neuroinflammation-induced glial scarring via rescuing Arf and Rho GAP adapter protein 3 expressions after nerve injury.
Activation of glucagon-like peptide-1 receptor in microglia attenuates neuroinflammation-induced glial scarring via rescuing Arf and Rho GAP adapter protein 3 expressions after nerve injury.
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小胶质细胞中胰高血糖素样肽-1受体的激活通过在神经损伤后挽救Arf和Rho GAP接头蛋白3的表达来减轻神经炎症诱导的神经胶质疤痕形成
DOI：
10.7150/ijbs.68974
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发表时间：
2022
影响因子：
9.2
通讯作者：
Hong X
中科院分区：
文献类型：
--
作者：
Qian Z;Chen H;Xia M;Chang J;Li X;Ye S;Wu S;Jiang S;Bao J;Wang B;Kong R;Zhang S;Zheng S;Cao X;Hong X
Rationale: The neuroinflammation is necessary for glial group initiation and clearance of damaged cell debris after nerve injury. However, the proinflammatory polarization of excessive microglia amplifies secondary injury via enhancing cross-talk with astrocytes and exacerbating neurological destruction after spinal cord injury (SCI). The glucagon-like peptide-1 receptor (GLP-1R) agonist has been previously shown to have a neuroprotective effect in neurodegeneration, whereas its potency in microglial inflammation after SCI is still unknown. Methods: The effect and mechanism of GLP-1R activation by exendin-4 (Ex-4) were investigated in in vitro cultured glial groups and in vivo in SCI mice. Alterations in the gene expression after GLP-1R activation in inflammatory microglia were measured using mRNA sequencing. The microglial polarization, neuroinflammatory level, and astrocyte reaction were detected by using western blotting, flow cytometry, and immunofluorescence. The recoveries of neurological histology and function were also observed using imaging and ethological examinations. Results: GLP-1R activation attenuated microglia-induced neuroinflammation by reversing M1 subtypes to M2 subtypes in vitro and in vivo. In addition, activation of GLP-1R in microglia blocked production of reactive astrocytes. We also found less neuroinflammation, reactive astrocytes, corrected myelin integrity, ameliorated histology, and improved locomotor function in SCI mice treated with Ex-4. Mechanistically, we found that Ex-4 rescued the RNA expression of Arf and Rho GAP adapter protein 3 (ARAP3). Knockdown of ARAP3 in microglia reversed activation of RhoA and the pharmacological effect of Ex-4 on anti-inflammation in vitro. Conclusion: Ex-4 exhibited a previously unidentified role in reducing reactive astrocyte activation by mediation of the PI3K/ARAP3/RhoA signaling pathway, by neuroinflammation targeting microglia, and exerted a neuroprotective effect post-SCI, implying that activation of GLP-1R in microglia was a therapeutical option for treatment of neurological injury.
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DOI：
10.1016/s0140-6736(17)31585-4
发表时间：
2017-10-07
期刊：
Lancet (London, England)
影响因子：
--
作者：
Athauda D;Maclagan K;Skene SS;Bajwa-Joseph M;Letchford D;Chowdhury K;Hibbert S;Budnik N;Zampedri L;Dickson J;Li Y;Aviles-Olmos I;Warner TT;Limousin P;Lees AJ;Greig NH;Tebbs S;Foltynie T
通讯作者：
Foltynie T
DOI：
10.1093/brain/aww039
发表时间：
2016-05
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Bartus K;Galino J;James ND;Hernandez-Miranda LR;Dawes JM;Fricker FR;Garratt AN;McMahon SB;Ramer MS;Birchmeier C;Bennett DL;Bradbury EJ
通讯作者：
Bradbury EJ
影响因子：
20.3
作者：
Gambardella, Laure;Anderson, Karen E.;Vermeren, Sonja
通讯作者：
Vermeren, Sonja
影响因子：
9.3
作者：
Kong, Fan-Qi;Zhao, Shu-Jie;Fan, Jin
通讯作者：
Fan, Jin
西他列汀通过 GLP-1R 诱导的抗细胞凋亡和促进脊髓损伤后轴突再生来改善功能恢复
影响因子：
5.3
作者：
Han, Wen;Li, Yao;Xiao, Jian
通讯作者：
Xiao, Jian