HMGB1 augments cognitive impairment in sepsis-associated encephalopathy by binding to MD-2 and promoting NLRP3-induced neuroinflammation
文献类型：期刊论文
| 作者 | Xiong, Yanan2; Yang, Jilin2; Tong, Haiyang1 ; Zhu, Chenting2; Pang, Yinhu2
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| 刊名 | PSYCHOGERIATRICS
 |
| 出版日期 | 2021-12-21 |
| ISSN号 | 1346-3500 |
| 关键词 | cognitive impairment HMGB1 MD-2 neuroinflammation NLRP3 sepsis-associated encephalopathy |
| DOI | 10.1111/psyg.12794 |
| 通讯作者 | Xiong, Yanan(xiongyanan0605@163.com) |
| 英文摘要 | Background Sepsis-associated encephalopathy (SAE) always manifests with severe inflammatory symptoms and cognitive impairment. High mobility group box 1 (HMGB1) is a pro-inflammatory cytokine. In this study we investigated the role of HMGB1 in SAE. Methods An SAE mouse model was established through cecal ligation and puncture surgery and then injected with adenovirus short hairpin RNA (Ad-sh)-HMGB1 or Ad-sh-myeloid differentiation protein (MD-2). The cognitive impairment and pathological injury in mice of different groups were evaluated using the Morris water maze experiment, Y-maze test, tail suspension test, fear conditioning test, and haematoxylin-eosin staining. The expressions of HMGB1 (fully reduced and disulfide (ds)HMGB1), MD-2, and NLRP3 in SAE mice were determined. Then, levels of inflammatory cytokines were measured. The binding relation between HMGB1 and MD-2 was predicted and certified. Additionally, MD-2 was downregulated to verify the role of the binding of HMGB1 and MD-2 in neuroinflammation and cognitive impairment in SAE. Results Expressions of HMGB1, MD-2, NLRP3, and inflammatory cytokines were enhanced in the SAE mouse model, which were in parallel with impaired cognitive function. HMGB1 silencing resulted in downregulated NLRP3 expression and alleviated neuroinflammation and cognitive impairment in SAE mice. Mechanically, dsHMGB1 bound to MD-2 to activate NLRP3, thereby exacerbating neuroinflammation and cognitive impairment in SAE mice. The limited binding of HMGB1 and MD-2 downregulated NLRP3 expression to alleviate neuroinflammation and cognitive impairment in SAE mice. Conclusion HMGB1 was overexpressed in SAE, and dsHMGB1 bound to MD-2 to activate NLRP3 inflammasome, inducing neuroinflammation and cognitive impairment in SAE. |
| WOS关键词 | TARGET |
| WOS研究方向 | Geriatrics & Gerontology ; Psychiatry |
| 语种 | 英语 |
| 出版者 | WILEY |
| WOS记录号 | WOS:000731907300001 |
| 源URL | [http://ir.hfcas.ac.cn:8080/handle/334002/126928]  |
| 专题 | 中国科学院合肥物质科学研究院 |
| 通讯作者 | Xiong, Yanan |
| 作者单位 | 1.Chinese Acad Sci, Hefei Inst Phys Sci, Hefei, Peoples R China 2.Tongji Univ, Sch Med, Shanghai Tongji Hosp, Dept Emergency, 389 Xincun Rd, Shanghai 200092, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xiong, Yanan,Yang, Jilin,Tong, Haiyang,et al. HMGB1 augments cognitive impairment in sepsis-associated encephalopathy by binding to MD-2 and promoting NLRP3-induced neuroinflammation[J]. PSYCHOGERIATRICS,2021. |
| APA | Xiong, Yanan,Yang, Jilin,Tong, Haiyang,Zhu, Chenting,&Pang, Yinhu.(2021).HMGB1 augments cognitive impairment in sepsis-associated encephalopathy by binding to MD-2 and promoting NLRP3-induced neuroinflammation.PSYCHOGERIATRICS. |
| MLA | Xiong, Yanan,et al."HMGB1 augments cognitive impairment in sepsis-associated encephalopathy by binding to MD-2 and promoting NLRP3-induced neuroinflammation".PSYCHOGERIATRICS (2021). |
入库方式： OAI收割
来源：合肥物质科学研究院
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