Disruption of C/EBP beta-Clec7a axis exacerbates neuroinflammatory injury via NLRP3 inflammasome-mediated pyroptosis in experimental neuropathic pain
文献类型：期刊论文
| 作者 | Wu, Dan1; Zhang, Yanqiong1; Zhao, Chunhui1; Li, Qiuyue1; Zhang, Junhong1; Han, Jiaxin2; Xu, Zhijian2 ; Li, Junfang1; Ma, Yan1; Wang, Ping1,2
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| 刊名 | JOURNAL OF TRANSLATIONAL MEDICINE
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| 出版日期 | 2022-12-12 |
| 卷号 | 20期号:1页码:19 |
| 关键词 | C/EBP beta-Clec7a axis Neuroinflammation Neuropathic Pain NLRP3 Inflammasome-mediated Pyroptosis |
| DOI | 10.1186/s12967-022-03779-9 |
| 通讯作者 | Xu, Haiyu(hyxu@icmm.ac.cn) |
| 英文摘要 | Background: Growing evidence shows that C-Type Lectin Domain Containing 7A (Clec7a) may be involved into neuroinflammatory injury of various neurological diseases. However, its roles in neuropathic pain remain unclear. Methods: A chronic constriction injury (CCI) rat model was constructed, and gene expression profilings in spinal cord tissues of CCI-insulted rats were detected by both microarray and RNA-seq studies. A series of bioinformatics analyses identified C/EBP beta-Clec7a to be a candidate axis involved into neuropathic pain. Then, its roles in mechanical allodynia, and pathological and molecular changes during CCI progression were determined by various gain-of-function and loss-of-function experiments in vivo and in vitro. Results: Significant upregulation of Clec7a at both mRNA and protein levels were verified in spinal cord tissues of CCI-insulted rats. Clec7a knockdown markedly attenuated CCI-induced mechanical allodynia, obstructed Syk, ERK and JNK phosphorylation, inhibited NLRP3 inflammasome and caspase-1 activation, GSDMD cleavage, and consequently reduced the release of pro-inflammatory cytokines (all P < 0.05). Mechanically, the rat Clec7a promoter was predicted to bind with transcription factor C/EBP beta, confirmed by Luciferase assay and ChIP-qPCR. Both in vivo and in vitro assays demonstrated that C/EBP beta knockdown significantly suppressed CCI- or LPS/ATP-induced Clec7a upregulation, and subsequently reduced Syk, ERK and JNK phosphorylation, NLRP3 oligomerization, caspase-1 activation, GSDMD expression and pyroptosis, which were markedly reversed by the co-transfection of Clec7a expression vector. Conclusions: This pre-clinical investigation reveals that C/EBP beta-Clec7a axis may be a potential target for relieving neuropathic pain through alleviating neuroinflammation, paving its way for clinical translation as a promising approach for neuropathic pain therapy. |
| WOS关键词 | PATHOLOGICAL PAIN ; C/EBP-BETA ; IMMUNE ; EXPRESSION ; DECTIN-1 |
| 资助项目 | Scientific and technological innovation project of China Academy of Chinese Medical Sciences ; National Natural Science Foundation of China ; National Key Research and Development Program of China ; Beijing Municipal Natural Science Foundation ; [CI2021A04904] ; [CI2021B015] ; [81830111] ; [2018YFC1705201] ; [7212186] |
| WOS研究方向 | Research & Experimental Medicine |
| 语种 | 英语 |
| WOS记录号 | WOS:000897981600004 |
| 出版者 | BMC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/304180]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Xu, Haiyu |
| 作者单位 | 1.China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China 3.China Acad Chinese Med Sci, Natl Med Prod Adm, Key Lab Res & Evaluat Tradit Chinese Med, Beijing 100700, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wu, Dan,Zhang, Yanqiong,Zhao, Chunhui,et al. Disruption of C/EBP beta-Clec7a axis exacerbates neuroinflammatory injury via NLRP3 inflammasome-mediated pyroptosis in experimental neuropathic pain[J]. JOURNAL OF TRANSLATIONAL MEDICINE,2022,20(1):19. |
| APA | Wu, Dan.,Zhang, Yanqiong.,Zhao, Chunhui.,Li, Qiuyue.,Zhang, Junhong.,...&Xu, Haiyu.(2022).Disruption of C/EBP beta-Clec7a axis exacerbates neuroinflammatory injury via NLRP3 inflammasome-mediated pyroptosis in experimental neuropathic pain.JOURNAL OF TRANSLATIONAL MEDICINE,20(1),19. |
| MLA | Wu, Dan,et al."Disruption of C/EBP beta-Clec7a axis exacerbates neuroinflammatory injury via NLRP3 inflammasome-mediated pyroptosis in experimental neuropathic pain".JOURNAL OF TRANSLATIONAL MEDICINE 20.1(2022):19. |
入库方式： OAI收割
来源：上海药物研究所
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