The identification of factor (s) which regulate individual radiosensitivity of human hematopoietic stem/progenitor cells and its application

人造血干/祖细胞个体放射敏感性调节因子的鉴定及其应用

• 批准号: 21390336
• 负责人: KASHIWAKURA Ikuo
• 金额: $ 6.99万
• 依托单位: Hirosaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21390336/
• 关键词: 造血幹細胞; 放射線; 遺伝子; 個体差

The purpose of this study was to clarify the individual radiosensitivity of human hematopoietic stem/progenitor cells and the relation between the characters of cell surface antigens, proliferative potentials and gene expressions, thus identifying what is the factor (s) to regulate the individual radiosensitivity of human hematopoietic stem cells. The following points were revealed.1. It suggest that the radiosensitivity of individual hematopoietic stem/progenitor cells (HSPCs) is related to the number of progenitor cells in the CD34^+ cells especially dependent on the presence of immature HSPCs such as Tie-2^+ cells.2. The mRNA expression of Nrf2 target genes such as HO-1, FTH1, NQO1, GSR and TXNRD1 was significantly increased after 2 Gy X irradiation. A statistically significant negative correlation was observed between the surviving fraction of HSPCs and the intrinsic NQO1 mRNA expression, indicating that HSPCs in which NQO1 mRNA levels are low may also be radioresistant. The present results suggest that the antioxidant system associated with Nrf2 is involved in the radiosensitivity of HSPCs.3. A significant correlation was observed between the surviving fraction of hematopoietic progenitor cells obtained after 0.5 Gy irradiation and the age of the blood donors. In particular, this correlation was more evident in males, with a correlation coefficient of-0.318 (P=0.043). A correlation between the individual responsiveness of hematopoietic progenitor cells to ionizing irradiation, particularly to a low-dose of irradiation (such as 0.5 Gy), and aging has been established.

本研究的目的是阐明人造血干/祖细胞的个体辐射敏感性及其与细胞表面抗原特性、增殖潜能和基因表达的关系，从而确定调节人造血干/祖细胞个体辐射敏感性的因素。揭示了以下几点。1.提示单个造血干/祖细胞（HSPCs）的辐射敏感性与CD 34 ^+细胞中祖细胞的数量有关，尤其依赖于Tie-2^+等未成熟HSPCs的存在. 2戈伊X射线照射后，HO-1、FTH 1、NQO 1、GSR和TXNRD 1等Nrf 2靶基因的mRNA表达明显增加。HSPCs的存活分数与内在NQO 1 mRNA表达之间存在统计学显著负相关，表明NQO 1 mRNA水平低的HSPCs也可能具有放射抗性。本研究结果提示，与Nrf 2相关的抗氧化系统参与了HSPCs的放射敏感性. 0.5戈伊照射后获得的造血祖细胞存活分数与献血者的年龄之间存在显着相关性。特别是，这种相关性在男性中更为明显，相关系数为-0.318（P=0.043）。造血祖细胞对电离辐射，特别是对低剂量辐射（如0.5戈伊）的个体响应性与衰老之间的相关性已经建立。

项目成果

Radiosensitivity of human hematopoietic stem/progenitor cells

人类造血干/祖细胞的放射敏感性

• 发表时间: 2012
• 作者: I.Kashiwakura;et al.
• 通讯作者: et al.

緑膿菌Quorum Sensing撹乱化合物のヒト口腔癌細胞増殖抑制作用と放射線増感作用

铜绿假单胞菌群体感应干扰化合物的人口腔癌细胞增殖抑制和放射增敏作用

• 发表时间: 2009
• 作者: 柏倉幾郎;他
• 通讯作者: 他

Individual radiation exposure dose due to support activities at safe shelters in Fukushima Prefecture.

• DOI: 10.1371/journal.pone.0027761
• 发表时间: 2011
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Monzen S;Hosoda M;Tokonami S;Osanai M;Yoshino H;Hosokawa Y;Yoshida MA;Yamada M;Asari Y;Satoh K;Kashiwakura I
• 通讯作者: Kashiwakura I

Involvement of mitochondrial function in radiosensitivity of human hematopoietic stem cells

线粒体功能参与人造血干细胞放射敏感性

• 发表时间: 2010
• 作者: Yukiko Kaneyuki;Kenji Takahashi and Ikuo Kashiwakura
• 通讯作者: Kenji Takahashi and Ikuo Kashiwakura

白血病細胞におけるlaminin receptorの発現とepigallocatechin-3-gallate(EGCG)に対する感受性

白血病细胞中层粘连蛋白受体的表达及对表没食子儿茶素-3-没食子酸酯（EGCG）的敏感性

• 发表时间: 2009
• 作者: 柏倉幾郎;他
• 通讯作者: 他