Matrilin-3 supports neuroprotection in ischemic stroke by suppressing astrocyte-mediated neuroinflammation
Xianyong Zhou, Yongming Zhu, De-fei 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
Abstract
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.