The influence of 3,3',5-triiodo-L-thyronine on human haematopoiesis
The influence of 3,3',5-triiodo-L-thyronine on human haematopoiesis
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DOI：
10.1111/j.1365-2184.2007.00435.x
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发表时间：
2007-06-01
影响因子：
8.5
通讯作者：
Machalinski, B.
中科院分区：
文献类型：
--
作者：
Grymula, K.;Paczkowska, E.;Machalinski, B.
目的：甲状腺激素介导人类许多生理和发育功能。3，3 '，5-三碘-L-甲状腺原氨酸（T3）在正常人造血中的作用在细胞和分子水平上尚未确定。本研究揭示了人类造血系统可能直接依赖于T3的影响。材料与方法：采用RT-PCR方法检测了人脐血、外周血和骨髓CD 34（+）富集祖细胞中TR α 1和TR β 1基因mRNA水平的表达。此外，我们进行了Western印迹，以证明TR α 1和TR β 1在人脐带血、外周血和骨髓CD 34（+）细胞中的蛋白水平上表达。此外，将检查的细胞群体在无血清条件下暴露于剂量不断增加的T3，随后通过采用膜联蛋白V染色和末端脱氧核苷酸转移酶介导的dUTP缺口末端标记方法，研究甲基纤维素培养物中粒细胞-巨噬细胞集落形成单位和红细胞爆发形成单位的克隆性生长以及细胞凋亡水平。我们研究了受检细胞中凋亡相关Bax和抗凋亡Bcl-2和Bcl-x（L）基因的表达水平。结果如下：我们发现，暴露于高于和低于正常浓度的甲状腺激素显着影响克隆形成和诱导人造血祖细胞凋亡。结论：这项研究扩大了对甲状腺疾病在正常人造血中作用的理解，并表明T3对这一过程的直接影响。
Objectives: Thyroid hormones mediate many physiological and developmental functions in humans. The role of the 3,3',5-triiodo-L-thyronine (T3) in normal human haematopoiesis at the cellular and molecular levels has not been determined. In this study, it was revealed that the human haematopoietic system might be directly depended on T3 influence. Materials and methods: We detected the TR alpha 1 and TR beta 1 gene expression at the mRNA level in human cord blood, peripheral blood and bone marrow CD34(+)-enriched progenitor cells, using the RT-PCR method. Furthermore, we performed Western blotting to prove TR alpha 1 and TR beta 1 expression occurs at the protein level in human cord blood, peripheral blood and bone marrow CD34(+) cells. In addition, the examined populations of cells were exposed in serum-free conditions to increasing doses of T3 and were subsequently investigated for clonogenic growth of granulocyte-macrophage colony-forming unit and erythrocyte burst-forming unit in methylcellulose cultures, and for the level of apoptosis, by employing annexin V staining and the terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling method. We investigated expression levels of apoptosis-related Bax and antiapoptotic Bcl-2 and Bcl-x(L) genes in the examined cells. Results: We found that exposure to higher and lower than normal concentration of thyroid hormone significantly influenced clonogenecity and induced apoptosis in human haematopoietic progenitor cells. Conclusions: This study expands the understanding of the role of thyroid disorders in normal human haematopoiesis and indicates a direct influence of T3 on this process.