Differential expression and regulatory roles of FABP5 and FABP7 in oligodendrocyte lineage cells
Differential expression and regulatory roles of FABP5 and FABP7 in oligodendrocyte lineage cells
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DOI：
10.1007/s00441-013-1730-7
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发表时间：
2013-12-01
影响因子：
3.6
通讯作者：
Owada, Yuji
中科院分区：
文献类型：
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作者：
Sharifi, Kazem;Ebrahimi, Majid;Owada, Yuji
脂肪酸结合蛋白(FABP)是细胞内的关键分子，参与脂肪酸的摄取、运输和储存，并参与信号转导和基因转录。然而，对它们在少突胶质细胞谱系中的表达和功能知之甚少。本研究采用免疫荧光对抗染色方法，观察了FABP5和FABP7在成年小鼠大脑皮质和穹隆体少突胶质细胞系细胞、混合皮质和少突胶质细胞系细胞中的表达。在所有设置中，在NG2(+)/PDGFRα(+)少突胶质前体细胞(OPC)中均检测到FABP7的表达，但不表达FABP5。在不表达FABP7的成熟CC1(+)/MBP+少突胶质细胞中检测到FABP5。对培养的OPC的分析表明，与野生型(WT)OPC相比，FABP7敲除(KO)OPC的数量和BrdU摄取显著减少。在少突胶质细胞分化培养液中，FABP7-KO OPC分化为O4(+)少突胶质细胞的比例明显降低。FABP7-KO和FABP5-KO中成熟的MBP+少突胶质细胞占O4(+)/MBP+少突胶质细胞的比例明显低于WT细胞。在FABP5-KO中，具有膜片形态的终末成熟少突胶质细胞的百分比明显低于WT细胞群体。因此，FABP7和FABP5在少突胶质细胞系细胞中差异表达，并调节其增殖和/或分化。我们的发现提示FABP7和FABP5参与了脱髓鞘障碍、神经精神障碍和胶质瘤的病理生理学过程，而OPC/少突胶质细胞在这些疾病中发挥了核心作用。
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(+)/PDGFR alpha(+) 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.