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The critical role of MLKL in hemorrhagic stroke and the therapeutic potential of its associated protein network

文献类型：期刊论文

作者Wang, Yi7,8,9; Xu, Moran6; Zuo, Xiaoli7; Wang, Sheng6; Yu, Yong5; Gao, Zhaobing4,7; Qie, Jingbo2,3; Jiang, Ye1; Huang, Fang8,9; Xia, Bingqing4,7
刊名FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
出版日期2025-01-20
卷号12页码:12
关键词mlkl ICH hemorrhagic stroke neuroinflammation LC-MS/MS
ISSN号2296-634X
DOI10.3389/fcell.2024.1509877
英文摘要Introduction Mixed Lineage Kinase Domain-Like Protein (MLKL), as the executor of necroptosis and a critical factor in the inflammation, has been shown to be associated with the progression of hemorrhagic stroke. Studies identified MLKL is a promoting factor in this process, suggesting its potential as a therapeutic target to mitigate posthemorrhagic stroke damage. However, the mechanisms by which MLKL functions in the process of intracerebral hemorrhage (ICH)-induced damage remain unclear.Methods Here, we explored the correlation between MLKL and pathological damage in ICH patients through histopathological staining and RT-qPCR. Furthermore, we established an intracerebral hemorrhage model by collagenase IV injection in WT and Mlkl-/- mice. Subsequently, we investigated the impact of MLKL knockout on ICH pathological damage through behavioral tests, Western blotting, and RT-qPCR. Finally, we performed a proteomic analysis via LC-MS/MS to explore the potential interacting proteins of MLKL in the progression of ICH.Results We found that MLKL is highly expressed in the brain tissue of ICH patients and is positively correlated with the extent of injury. However, we found that Mlkl knockout alone was insufficient to fully reverse neuroinflammation and pathological damage. Although Mlkl knockout has a limited effect on alleviating ICH damage, proteomics results indicate that MLKL can mitigate changes in proteins associated with inflammation, metabolism, and coagulation pathways, suggesting that MLKL may exert its effects through these pathways.Discussion In summary, our results suggest that although MLKL is associated with the progression of ICH, single knockout of Mlkl is insufficient to fully reverse the pathological damage of ICH. Proteomic analysis indicates that co-targeting MLKL and its associated protein network may yield better therapeutic outcomes for hemorrhagic stroke.
WOS关键词MIXED LINEAGE KINASE ; INTRACEREBRAL HEMORRHAGE ; PHOSPHORYLATION
资助项目Fund of Youth Innovation Promotion Association[Y2023078] ; National Natural Science Foundation of China[92169202] ; National Natural Science Foundation of China[82341058] ; Fund of Shanghai Sailing Program[23YF1433100] ; Fund of Shanghai Science and Technology Innovation Action Plan[20ZR1474200] ; Shanghai Rising-Star Program[22QA1411000] ; Natural Science Foundation of Shanghai[22ZR1474000]
WOS研究方向Cell Biology ; Developmental Biology
语种英语
WOS记录号WOS:001411064100001
出版者FRONTIERS MEDIA SA
源URL[http://119.78.100.183/handle/2S10ELR8/315980]  
专题新药研究国家重点实验室
通讯作者Qie, Jingbo; Jiang, Ye; Huang, Fang; Xia, Bingqing
作者单位1.Fudan Univ, Minhang Hosp, Dept Neurosurg, Shanghai, Peoples R China
2.Fudan Univ, Inst Biomed Sci, Shanghai, Peoples R China
3.Fudan Univ, Shanghai Peoples Hosp 5, Shanghai, Peoples R China
4.Univ Chinese Acad Sci, Beijing, Peoples R China
5.Fudan Univ, Zhongshan Hosp, Natl Med Ctr, Dept Neurosurg, Shanghai, Peoples R China
6.Fudan Univ, Huashan Hosp, Inst Biomed Sci, Dept Digest Dis, Shanghai, Peoples R China
7.Chinese Acad Sci, Shanghai Inst Mat Med, Stake Key Lab Drug Res, Shanghai, Peoples R China
8.Fudan Univ, Inst Brain Sci, MOE Frontiers Ctr Brain Sci, Shanghai, Peoples R China
9.Fudan Univ, Jingan Dist Ctr Hosp Shanghai, Inst Brain Sci, State Key Lab Med Neurobiol,Dept Translat Neurosci, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Wang, Yi,Xu, Moran,Zuo, Xiaoli,et al. The critical role of MLKL in hemorrhagic stroke and the therapeutic potential of its associated protein network[J]. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY,2025,12:12.
APA Wang, Yi.,Xu, Moran.,Zuo, Xiaoli.,Wang, Sheng.,Yu, Yong.,...&Xia, Bingqing.(2025).The critical role of MLKL in hemorrhagic stroke and the therapeutic potential of its associated protein network.FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY,12,12.
MLA Wang, Yi,et al."The critical role of MLKL in hemorrhagic stroke and the therapeutic potential of its associated protein network".FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY 12(2025):12.

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来源：上海药物研究所

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