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FABP5 和 FABP7 在少突胶质细胞谱系细胞中的差异表达和调控作用。

Differential expression and regulatory roles of FABP5 and FABP7 in oligodendrocyte lineage cells.

机构信息

Department of Organ Anatomy, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, 755-8505, Japan.

出版信息

Cell Tissue Res. 2013 Dec;354(3):683-95. doi: 10.1007/s00441-013-1730-7. Epub 2013 Oct 11.

Abstract

Fatty-acid-binding proteins (FABPs) are key intracellular molecules involved in the uptake, transportation and storage of fatty acids and in the mediation of signal transduction and gene transcription. However, little is known regarding their expression and function in the oligodendrocyte lineage. We evaluate the in vivo and in vitro expression of FABP5 and FABP7 in oligodendrocyte lineage cells in the cortex and corpus callosum of adult mice, mixed cortical culture and oligosphere culture by immunofluorescent counter-staining with major oligodendrocyte lineage markers. In all settings, FABP7 expression was detected in NG2(+)/PDGFRα(+) oligodendrocyte progenitor cells (OPCs) that did not express FABP5. FABP5 was detected in mature CC1(+)/MBP(+) oligodendrocytes that did not express FABP7. Analysis of cultured OPCs showed a significant decrease in the population of FABP7-knockout (KO) OPCs and their BrdU uptake compared with wild-type (WT) OPCs. Upon incubation of OPCs in oligodendrocyte differentiation medium, a significantly lower percentage of FABP7-KO OPCs differentiated into O4(+) oligodendrocytes. The percentage of mature MBP(+) oligodendrocytes relative to whole O4(+)/MBP(+) oligodendrocytes was significantly lower in FABP7-KO and FABP5-KO than in WT cell populations. The percentage of terminally mature oligodendrocytes with membrane sheet morphology was significantly lower in FABP5-KO compared with WT cell populations. Thus, FABP7 and FABP5 are differentially expressed in oligodendrocyte lineage cells and regulate their proliferation and/or differentiation. Our findings suggest the involvement of FABP7 and FABP5 in the pathophysiology of demyelinating disorders, neuropsychiatric disorder and glioma, conditions in which OPCs/oligodendrocytes play central roles.

摘要

脂肪酸结合蛋白(FABP)是参与脂肪酸摄取、运输和储存以及信号转导和基因转录调节的关键细胞内分子。然而,关于它们在少突胶质细胞谱系中的表达和功能知之甚少。我们通过免疫荧光细胞化学双重染色,用主要的少突胶质细胞谱系标志物,评估 FABP5 和 FABP7 在成年小鼠大脑皮质和胼胝体中的少突胶质细胞谱系细胞、混合皮质培养物和寡球培养物中的体内和体外表达。在所有情况下,FABP7 在不表达 FABP5 的 NG2(+) / PDGFRα(+)少突胶质前体细胞(OPC)中均有表达。FABP5 在不表达 FABP7 的成熟 CC1(+) / MBP(+)少突胶质细胞中被检测到。对培养的 OPC 分析表明,与野生型(WT)OPC 相比,FABP7 敲除(KO)OPC 的数量及其 BrdU 摄取明显减少。在少突胶质细胞分化培养基中孵育 OPC 后,FABP7-KO OPC 分化为 O4(+)少突胶质细胞的比例显著降低。与 WT 细胞群体相比,FABP7-KO 和 FABP5-KO 细胞中成熟 MBP(+)少突胶质细胞的比例相对 O4(+) / MBP(+)少突胶质细胞的比例显著降低。FABP5-KO 细胞中具有膜片形态的终末成熟少突胶质细胞的比例明显低于 WT 细胞群体。因此,FABP7 和 FABP5 在少突胶质细胞谱系细胞中差异表达,并调节其增殖和/或分化。我们的研究结果表明,FABP7 和 FABP5 参与脱髓鞘疾病、神经精神疾病和神经胶质瘤的病理生理学,在这些疾病中,OPC/少突胶质细胞起着核心作用。

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