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IGFBP-7 通过调控 Wnt/β-Catenin 信号通路抑制少突胶质前体细胞的分化。

IGFBP-7 inhibits the differentiation of oligodendrocyte precursor cells via regulation of Wnt/β-Catenin signaling.

机构信息

Department of Intensive Care Unit, The First Hospital of Jilin University, Changchun, China.

Jinzhou Maternal and Children Healthy Care Hospital, Jinzhou, China.

出版信息

J Cell Biochem. 2018 Jun;119(6):4742-4750. doi: 10.1002/jcb.26654. Epub 2018 Feb 28.

Abstract

Oligodendrocytes (OLs) are glial cells that form myelin sheaths in the central nervous system. Myelin sheath plays important role in nervous system and loss of it in neurodegenerative diseases can lead to impairment of movement. Understanding the signals and factors that regulate OL differentiation can help to address novel strategies for improving myelin repair in neurodegenerative diseases. The aim of this study was to investigate the role of insulin-like growth factor-binding proteins 7 (IGFBP-7) in differentiating OL precursor cells (OPCs). It was found that oligodendrocyte precursors undergoing differentiation were accompanied by selective expression of IGFBP-7. In addition, knockdown of IGFBP-7 promoted differentiation of oligodendrocytes and increased formation of myelin in cultured cells. In contrast, excessive expression of IGFBP-7 inhibited differentiation of oligodendrocytes. Furthermore, overexpression of IGFBP-7 in oligodendrocyte precursor cells increased transcription of Wnt target genes and promoted β-Catenin nuclear translocation. These findings suggest that IGFBP-7 negatively regulates differentiation of oligodendrocyte precursor cells via regulation of Wnt/β-Catenin signaling.

摘要

少突胶质细胞(OLs)是形成中枢神经系统髓鞘的神经胶质细胞。髓鞘在神经系统中起着重要作用,在神经退行性疾病中丧失髓鞘会导致运动功能障碍。了解调节 OL 分化的信号和因素有助于为神经退行性疾病中的髓鞘修复提供新的策略。本研究旨在探讨胰岛素样生长因子结合蛋白 7(IGFBP-7)在 OL 前体细胞(OPC)分化中的作用。研究发现,分化中的少突胶质前体细胞伴随着 IGFBP-7 的选择性表达。此外,IGFBP-7 的敲低促进了少突胶质细胞的分化,并增加了培养细胞中髓鞘的形成。相反,IGFBP-7 的过度表达抑制了少突胶质细胞的分化。此外,在少突胶质前体细胞中过表达 IGFBP-7 会增加 Wnt 靶基因的转录,并促进 β-连环蛋白核易位。这些发现表明,IGFBP-7 通过调节 Wnt/β-连环蛋白信号通路负调控少突胶质前体细胞的分化。

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