TNF-like weak inducer of apoptosis / nuclear factor κB axis feedback loop promotes spinal cord injury by inducing astrocyte activation.
TNF-like weak inducer of apoptosis / nuclear factor κB axis feedback loop promotes spinal cord injury by inducing astrocyte activation.
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TNF样弱凋亡诱导剂/核因子γB轴反馈环路通过诱导星形胶质细胞激活促进脊髓损伤
DOI：
10.1080/21655979.2022.2068737
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发表时间：
2022-05
期刊：
影响因子：
4.9
通讯作者：
中科院分区：
文献类型：
--
作者：
摘要非经典信号通路被证实是星形胶质细胞渗透性扩张或增殖的有效位点，促进非神经脊髓损伤（SCI）区轴突再生。然而，诱导星形胶质细胞自噬性细胞死亡的相关信号通路及其与TNF样弱凋亡诱导因子/核因子κB（TWEAK/NF-κB）轴相关的功能仍不清楚。根据艾伦的模型，通过垂直撞击脊髓建立SCI模型。从提取自SCI或正常C57 BL/6新生小鼠的脊髓组织的脊髓细胞制备星形胶质细胞和神经元细胞。共培养星形胶质细胞和神经元后，CCK-8，透射电子显微镜（TEM）和蛋白质印迹法测定细胞活力和自噬。通过qRT-PCR、Western blot、免疫荧光和ELISA检测TWEAK、NF-κB和炎性细胞因子的表达。染色质免疫沉淀法（Chromatin immunoprecipitation，CHIP）检测TWEAK与NF-κB的相互作用。我们的结果表明，敲低TWEAK和NF-κB抑制TNF-α/IL-1β的高水平分泌，部分被添加Rap抵消。TWEAK/NF-κB是脊髓损伤后星形胶质细胞增殖和自噬的正相关反馈环。抑制星形胶质细胞的过度生长有利于神经元的生长。总的来说，我们的研究结果表明，TWEAK/NF-κB通路可能通过诱导星形胶质细胞活化而作为SCI的正性调节剂，为SCI治疗提供了新的见解。图形摘要
ABSTRACT Non-canonical signaling pathways have been proved to act as potent sites of astrocytes osmotic expanding or proliferation, which promotes the regeneration of axons in areas with non-neural spinal cord injury (SCI). However, the relevant signal pathway that induces autophagic cell death in astrocytes and its function relative to the TNF-like weak inducer of apoptosis/nuclear factor κB (TWEAK/NF-κB) axis remains elusive. The SCI model was established by vertically striking the spinal cord according to Allen’s model. Astrocytes and neuronal cells were prepared from spinal cells extracted from spinal cord tissues of SCI or normal C57BL/6 newborn mice. After co-culturing astrocytes and neurons, cell viability and autophagy were determined by CCK-8, transmission electron microscopy (TEM), and western blot. The expression of TWEAK, NF-κB and inflammatory cytokines was confirmed by qRT-PCR, western blot, Immunofluorescence and ELISA assay. Chromatin immunoprecipitation (CHIP) was used to evaluate the interaction between TWEAK and NF-κB. Our results demonstrated that knockdown of TWEAK and NF-κB inhibited secretion of high levels of TNF-α/IL-1β, partially counteracted by adding Rap. TWEAK/NF-κB was the positive correlation feedback loop regulating the proliferation and autophagy of astrocytes involved in SCI. Moreover, restraining the excess growth of astrocytes was beneficial to the growth of neurons. Collectively, our findings illustrated that the TWEAK/NF-κB pathway might act as a positive modulator of SCI by inducing astrocyte activation, shedding new insights for SCI treatment. Graphical Abstract
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DOI：
10.15252/embj.201798697
发表时间：
2018-08-15
期刊：
The EMBO journal
影响因子：
--
作者：
Ouali Alami N;Schurr C;Olde Heuvel F;Tang L;Li Q;Tasdogan A;Kimbara A;Nettekoven M;Ottaviani G;Raposo C;Röver S;Rogers-Evans M;Rothenhäusler B;Ullmer C;Fingerle J;Grether U;Knuesel I;Boeckers TM;Ludolph A;Wirth T;Roselli F;Baumann B
通讯作者：
Baumann B
影响因子：
20.3
作者：
Chopra, Martin;Brandl, Andreas;Wajant, Harald
通讯作者：
Wajant, Harald
影响因子：
6.2
作者：
Goulao, Miguel;Ghosh, Biswarup;Lepore, Angelo C.
通讯作者：
Lepore, Angelo C.
DOI：
10.1196/annals.1397.069
发表时间：
2007-01-01
期刊：
SIGNAL TRANSDUCTION PATHWAYS, PT D
影响因子：
--
作者：
Bachmeier, Beatrice E.;Nerlich, Andreas G.;Boos, Norbert
通讯作者：
Boos, Norbert
纳米材料介导的自噬：生物医学中并存的危害和健康益处
影响因子：
10
作者：
Feng X;Zhang Y;Zhang C;Lai X;Zhang Y;Wu J;Hu C;Shao L
通讯作者：
Shao L