FGF2-Responsive Genes in human Dental Pulp Cells Assessed using a Rat Spinal Cord Injury Model
FGF2-Responsive Genes in human Dental Pulp Cells Assessed using a Rat Spinal Cord Injury Model
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使用大鼠脊髓损伤模型评估人牙髓细胞中的 FGF2 响应基因
DOI：
10.1007/s00774-018-0954-8
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
and Ken-ichi Tezuka
中科院分区：
文献类型：
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作者：
Ken Sugiyama;Kosuke Nagashima;Takahiro Miwa;Yuta Shimizu;Tomoko Kawaguchi;Kazuki Iida;Naritaka Tamaoki;Daijiro Hatakeyama;Hitomi Aoki;Chikara Abe;Hironobu Morita;Takahiro Kunisada;Toshiyuki Shibata;Hidefumi Fukumitsu;and Ken-ichi Tezuka
成年哺乳动物的中枢神经系统在脊髓损伤（SCI）后不会自行愈合。然而，随着细胞移植疗法的发展，SCI治疗最近得到了改善。我们最近报道，成纤维细胞生长因子 (FGF) 2 预处理的人牙髓细胞 (hDPC) 可以改善 SCI 大鼠模型的恢复。本研究旨在探讨FGF2预处理增强SCI疗效的机制；我们在 SCI 大鼠模型中筛选间充质干细胞标记物的存在及其功能后，选择了三个 hDPC 系，并使用运动功能量表的 Basso、Beattie 和 Bresnahan 评分、电生理学测试和形态学分析进行评估。我们通过这些品系中的基因表达分析鉴定了 FGF2 反应基因。 FGF2 治疗上调 GABRB1、MMP1 和 DRD2，这表明可能导致 SCI 或中枢神经系统。在对其他品系的扩展筛选中，GABRB1表现出相当独特且有趣的行为； GABRB1 对 FGF2 处理敏感性最低的两条细胞系在 SCI 模型中显示出极小的影响。这些发现提供了关于 FGF2 响应基因（尤其是 GABRB1）在使用经 FGF2 处理的 hDPC 进行 SCI 恢复中的作用的见解。
The central nervous system in adult mammals does not heal spontaneously after spinal cord injury (SCI). However, SCI treatment has been improved recently following the development of cell transplantation therapy. We recently reported that fibroblast growth factor (FGF) 2-pretreated human dental pulp cells (hDPCs) can improve recovery in a rat model of SCI. This study aimed to investigate mechanisms underlying the curative effect of SCI enhanced via FGF2 pretreatment; we selected three hDPC lines upon screening for the presence of mesenchymal stem cell markers and of their functionality in a rat model of SCI, as assessed using the Basso, Beattie, and Bresnahan score of locomotor functional scale, electrophysiological tests, and morphological analyses. We identified FGF2-responsive genes via gene expression analyses in these lines. FGF2 treatment upregulatedGABRB1,MMP1, andDRD2, which suggested to contribute to SCI or central the nervous system. In an expanded screening of additional lines,GABRB1displayed rather unique and interesting behavior; two lines with the lowest sensitivity ofGABRB1to FGF2 treatment displayed an extremely minor effect in the SCI model. These findings provide insights into the role of FGF2-responsive genes, especiallyGABRB1, in recovery from SCI, using hDPCs treated with FGF2.