神经保护
神经炎症
星形胶质细胞
细胞生物学
化学
信号转导
细胞外
炎症
神经科学
药理学
生物
免疫学
中枢神经系统
作者
Xianyong Zhou,Yong‐Ming Zhu,De-Fei Gao,Min Li,Liang Lin,Zhanxiang Wang,Huaping Du,Yuan Xu,Jin Liu,Yang He,Yi Guo,Shuai Wang,Shigang Qiao,Yuheng Bao,Yuan Liu,Huiling Zhang
出处
期刊:Cell Reports
[Elsevier]
日期:2024-04-01
卷期号:43 (4): 113980-113980
标识
DOI:10.1016/j.celrep.2024.113980
摘要
In the brain, the role of matrilin-3, an extracellular matrix component in cartilage, is unknown. Here, we identify that matrilin-3 decreased in reactive astrocytes but was unchanged in neurons after ischemic stroke in animals. Importantly, it declined in serum of patients with acute ischemic stroke. Genetic or pharmacological inhibition or supplementation of matrilin-3 aggravates or reduces brain injury, astrocytic cell death, and glial scar, respectively, but has no direct effect on neuronal cell death. RNA sequencing demonstrates that Matn3-/- mice display an increased inflammatory response profile in the ischemic brain, including the nuclear factor κB (NF-κB) signaling pathway. Both endogenous and exogenous matrilin-3 reduce inflammatory mediators. Mechanistically, extracellular matrilin-3 enters astrocytes via caveolin-1-mediated endocytosis. Cytoplasmic matrilin-3 translocates into the nucleus by binding to NF-κB p65, suppressing inflammatory cytokine transcription. Extracellular matrilin-3 binds to BMP-2, blocking the BMP-2/Smads pathway. Thus, matrilin-3 is required for astrocytes to exert neuroprotection, at least partially, by suppressing astrocyte-mediated neuroinflammation.
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