Matrilin-3 supports neuroprotection in ischemic stroke by suppressing astrocyte-mediated neuroinflammation

• DOI: 10.1016/j.celrep.2024.113980
• Publication Date: 2024-03-22T11:32:17Z
• Authors: Xianyong Zhou; Yongming Zhu; Defei Gao; Min Li; Liang Lin; Zhanxiang Wang; Huaping Du; Yuan Xu; Jin Liu; Yang He; Yi Guo; Shuai Wang; Shigang Qiao; Yingshi Bao; Yuan Liu; Huiling Zhang
• Keywords: Stroke

Highlights•Matrilin-3 decreases in both animal brains and patient serum with ischemic stroke•Matrilin-3 protects brain by suppressing astrocytic inflammation•Extracellular matrilin-3 enters astrocytes via CAV1-mediated endocytosis•Matrilin-3 binds to NF-κB p65 or extracellular BMP-2 inhibit neuroinflammationSummaryIn the brain, role of matrilin-3, an matrix component cartilage, is unknown. Here, we identify that decreased reactive but was unchanged neurons after stroke animals. Importantly, it declined patients acute stroke. Genetic pharmacological inhibition supplementation aggravates reduces injury, cell death, glial scar, respectively, has no direct effect on neuronal death. RNA sequencing demonstrates Matn3−/− mice display increased inflammatory response profile including nuclear factor κB (NF-κB) signaling pathway. Both endogenous exogenous reduce mediators. Mechanistically, caveolin-1-mediated endocytosis. Cytoplasmic translocates into nucleus binding p65, cytokine transcription. Extracellular BMP-2, blocking BMP-2/Smads Thus, required for exert neuroprotection, at least partially, astrocyte-mediated neuroinflammation.Graphical abstract