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小胶质细胞通过分泌骨桥蛋白促进神经前体细胞的增殖。

Microglia promote the proliferation of neural precursor cells by secreting osteopontin.

机构信息

Department of Molecular Pharmacology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo, 187-8502, Japan.

Department of Molecular Pharmacology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo, 187-8502, Japan.

出版信息

Biochem Biophys Res Commun. 2019 Jun 11;513(4):841-845. doi: 10.1016/j.bbrc.2019.04.076. Epub 2019 Apr 16.

Abstract

Microglia are central nervous system-resident immune cells that play a crucial role in brain development by interacting with neural precursor cells (NPCs). It has been reported that microglia regulate the number of NPC by phagocytosis, inducing apoptosis, and promoting proliferation. Microglia surrounding the subventricular zone express osteopontin (OPN) during brain development. The present study investigated the role of microglia in proliferation of NPCs in vitro, and identified the OPN receptor critical for proliferation of NPCs. Microglia co-cultured with NPCs in the presence of an OPN-neutralizing antibody resulted in OPN inhibition and reduced microglia-induced proliferation of NPCs. NPCs express integrin αvβ3, which has been identified as an OPN receptor. Cilengitide, an inhibitor of integrin αvβ3, also inhibited microglia-induced proliferation of NPCs. These results suggest that microglia promote the proliferation of NPCs via OPN-integrin αvβ3 signaling.

摘要

小胶质细胞是中枢神经系统驻留的免疫细胞,通过与神经前体细胞(NPC)相互作用,在大脑发育中发挥着关键作用。据报道,小胶质细胞通过吞噬作用、诱导细胞凋亡和促进增殖来调节 NPC 的数量。在大脑发育过程中,室下区周围的小胶质细胞表达骨桥蛋白(OPN)。本研究探讨了小胶质细胞在体外 NPC 增殖中的作用,并确定了增殖 NPC 所需的 OPN 受体。在存在 OPN 中和抗体的情况下,小胶质细胞与 NPC 共培养会导致 OPN 抑制和小胶质细胞诱导的 NPC 增殖减少。NPC 表达整合素 αvβ3,该整合素已被鉴定为 OPN 受体。整合素 αvβ3 的抑制剂 cilengitide 也抑制了小胶质细胞诱导的 NPC 增殖。这些结果表明,小胶质细胞通过 OPN-整合素 αvβ3 信号促进 NPC 的增殖。

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