Astrocytic CD24 Protects Neuron from Recombinant High-Mobility Group Box 1 Protein(rHMGB1)-Elicited Neuronal Injury.
Astrocytic CD24 Protects Neuron from Recombinant High-Mobility Group Box 1 Protein(rHMGB1)-Elicited Neuronal Injury.
复制标题
星形胶质细胞 CD24 保护神经元免受重组高迁移率族蛋白 1 (rHMGB1) 引起的神经元损伤
DOI：
10.3390/brainsci12091119
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发表时间：
2022-08-23
期刊：
影响因子：
3.3
通讯作者：
Hang, Chun-Hua
中科院分区：
文献类型：
--
作者：
Pang, Cong;Gao, Sen;Liu, Xun-Zhi;Li, Xiao-Jian;Peng, Zheng;Zhang, Hua-Sheng;Zhou, Yan;Chen, Xiang-Xin;Tao, Tao;Lu, Yue;Li, Wei;Hang, Chun-Hua
内源性宿主源分子损伤相关分子模式（DAMPs）可以诱导特异性膜系受体识别过度的非无菌炎症反应。在本研究中，我们旨在探讨DAMP分子HMGB1在星形胶质细胞介导的无菌神经炎症中的作用及其对神经元的影响。用rHMGB1刺激体外培养的星形胶质细胞，分别于6 h、12 h、24 h、36 h和48 h收获。采用实时定量聚合酶链反应（qPCR）、Western blot和免疫荧光法检测星形胶质细胞CD24的表达，电泳迁移位移法（EMSA）检测核因子κB （NF-κB）结合活性，qPCR检测促炎因子、肿瘤坏死因子-α (TNF-α)、白细胞介素1β (IL-1β)的表达。用相衬显微镜观察神经元形态。结果显示，rHMGB1刺激后，星形胶质细胞mRNA和CD24蛋白表达在24 h开始升高，36 h达到峰值，48 h保持升高，同时伴有NF-κB结合活性增强，TNF-α和IL-1β表达增强。此外，rHMGB1引起共培养神经元损伤，并在CD24敲低时聚集。综上所述，这些新发现表明rHMGB1可以促进星形细胞CD24的表达，抑制CD24的表达可能会聚集神经元损伤。
Endogenous host-derived molecules named damage-associated molecular patterns (DAMPs) can induce excessive non-sterile inflammatory responses on recognition of specific membrane-tethered receptors. Here in this study, we aimed to explore the role of DAMP molecule HMGB1 in astrocyte-mediated sterile neuroinflammation and the resultant influences on neurons. In vitro cultured astrocytes were challenged with rHMGB1 and then harvested at 6 h, 12 h, 24 h, 36 h, and 48 h, respectively. The astrocytic CD24 expression was determined by quantitative real-time polymerase chain reaction (qPCR), Western blot analysis and immunofluorescence, nuclear factor kappa B (NF-κB) binding activity was detected by electrophoretic mobility shift assay (EMSA), and the proinflammatory factors, tumor necrosis factor-α (TNF-α), and interleukin 1β (IL-1β), were measured by qPCR. The neuronal morphology was assessed with phase-contrast microscopy. The results showed that astrocytic mRNA and protein CD24 expression began to rise at 24 h, peaked at 36 h, and remained elevated at 48 h after rHMGB1 stimulation, accompanied with enhanced NF-κB binding activity and augmented expression of TNF-α and IL-1β. Furthermore, rHMGB1 caused cocultured neuron damage and was aggregated upon CD24 knockdown. Taken together, these novel findings suggested that rHMGB1 could promote astrocytic CD24 expression, the inhibition of which could aggregate neuronal damage.
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影响因子：
64.5
作者：
Saunders A;Macosko EZ;Wysoker A;Goldman M;Krienen FM;de Rivera H;Bien E;Baum M;Bortolin L;Wang S;Goeva A;Nemesh J;Kamitaki N;Brumbaugh S;Kulp D;McCarroll SA
通讯作者：
McCarroll SA
影响因子：
16.8
作者：
Liu Y;Chen GY;Zheng P
通讯作者：
Zheng P
影响因子：
16.2
作者：
Linnerbauer M;Wheeler MA;Quintana FJ
通讯作者：
Quintana FJ
影响因子：
64.8
作者：
Scaffidi, P;Misteli, T;Bianchi, ME
通讯作者：
Bianchi, ME
影响因子：
4.4
作者：
Pedrazzi, Marco;Patrone, Mauro;Melloni, Edon
通讯作者：
Melloni, Edon