Protease-activated receptor-1 negatively regulates proliferation of neural stem/progenitor cells derived from the hippocampal dentate gyrus of the adult mouse
Protease-activated receptor-1 negatively regulates proliferation of neural stem/progenitor cells derived from the hippocampal dentate gyrus of the adult mouse
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蛋白酶激活受体-1负向调节成年小鼠海马齿状回来源的神经干/祖细胞的增殖
DOI：
10.1016/j.jphs.2016.05.005
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发表时间：
2016
影响因子：
3.5
通讯作者：
Kiyokazu Ogita
中科院分区：
文献类型：
--
作者：
Masayuki Tanaka;Masanori Yoneyama;Tatsuo Shiba;Taro Yamaguchi;Kiyokazu Ogita
凝血酶激活蛋白酶激活受体（PAR）-1调节脑损伤后神经细胞的增殖。为了阐明PAR-1参与发生在成年海马的神经发生，我们研究了PAR-1是否调节来自小鼠海马齿状回的神经干/祖细胞（NPC）的增殖。NPC培养物表达PAR-1蛋白和编码所有PAR亚型的mRNA。将细胞直接暴露于凝血酶显著地减弱了细胞增殖而不引起细胞损伤。PAR拮抗剂RWJ 56110以及达比加群和4-（2-氨乙基）苯磺酰氟（AEBSF）（分别为选择性和非选择性凝血酶抑制剂）几乎完全消除了凝血酶诱导的衰减。预期PAR-1激动剂肽（AP）SFLLR-NH 2也抑制细胞增殖。细胞增殖不受PAR-1阴性对照肽RLLFT-NH 2的影响，RLLFT-NH 2是PAR-1的无活性肽。独立地，我们测定了AEBSF或AP体内处理对成年小鼠海马神经发生的影响。AEBSF的管理，而不是AP，显着增加了海马颗粒下区的新生成的细胞的数量。这些数据表明，PAR-1负调控成年神经发生在海马通过抑制增殖活性的NPC。
Thrombin-activated protease-activated receptor (PAR)-1 regulates the proliferation of neural cells following brain injury. To elucidate the involvement of PAR-1 in the neurogenesis that occurs in the adult hippocampus, we examined whether PAR-1 regulated the proliferation of neural stem/progenitor cells (NPCs) derived from the murine hippocampal dentate gyrus. NPC cultures expressed PAR-1 protein and mRNA encoding all subtypes of PAR. Direct exposure of the cells to thrombin dramatically attenuated the cell proliferation without causing cell damage. This thrombin-induced attenuation was almost completely abolished by the PAR antagonist RWJ 56110, as well as by dabigatran and 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF), which are selective and non-selective thrombin inhibitors, respectively. Expectedly, the PAR-1 agonist peptide (AP) SFLLR-NH2also attenuated the cell proliferation. The cell proliferation was not affected by the PAR-1 negative control peptide RLLFT-NH2, which is an inactive peptide for PAR-1. Independently, we determined the effect ofin vivotreatment with AEBSF or AP on hippocampal neurogenesis in the adult mouse. The administration of AEBSF, but not that of AP, significantly increased the number of newly-generated cells in the hippocampal subgranular zone. These data suggest that PAR-1 negatively regulated adult neurogenesis in the hippocampus by inhibiting the proliferative activity of the NPCs.