Clinical relevance of thyroid dysfunction in human haematopoiesis: biochemical and molecular studies
Clinical relevance of thyroid dysfunction in human haematopoiesis: biochemical and molecular studies
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DOI：
10.1530/eje-09-0875
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发表时间：
2010-02-01
影响因子：
5.8
通讯作者：
Machalinski, Boguslaw
中科院分区：
文献类型：
--
作者：
Kawa, Milosz Piotr;Grymula, Katarzyna;Machalinski, Boguslaw
目的：甲状腺疾病患者的血液学参数存在异常。尽管如此，甲状腺激素（THs）对人类造血作用的确切机制仍不完全清楚。 设计：分析THs通过TH受体（TR α-1和TR β-1）对甲状腺功能减退症和甲状腺功能亢进症患者造血的影响。方法：从人类CD34（+）富集的造血祖细胞（HPC）中获得TR基因在mRNA和蛋白质水平的表达。对甲状腺疾病患者和健康志愿者的外周血进行了分析。还研究了细胞群的粒细胞巨噬细胞集落形成单位和红细胞爆发形成单位（BFU-E）的克隆生长。通过膜联蛋白 V/碘化丙啶染色和定量 RT-PCR 测定细胞凋亡水平。结果：研究表明，甲状腺功能减退和甲状腺功能亢进会改变体内 HPC 中 TR 基因的表达。 TH 缺乏导致全血细胞计数和 BFU-E 克隆形成潜力下降。相比之下，甲状腺功能亢进患者的克隆生长和 BFU-E 数量增加，细胞周期调节基因（例如 PCNA 和细胞周期蛋白 D1）的表达显着升高。最后，检测到甲状腺功能减退症和甲状腺功能亢进症中富含 CD34(+) 的 HPC 的凋亡频率随着凋亡相关基因的调节而增加。结论：得出以下结论：i) 人类造血细胞中的 TR 表达取决于 TH 状态，ii) 甲状腺功能减退症和甲状腺功能亢进均显着影响富含 CD34(+) 的 HPC 的集落形成并诱导细胞凋亡，iii) TH 影响的分子机制造血作用可能为设计甲状腺疾病的新型治疗干预措施提供基础。
Objective: Abnormalities in haematological parameters have been noted in patients with thyroid diseases. Nevertheless, the exact mechanism of thyroid hormones' (THs) action on human haematopoiesis is still not entirely clear.Design: The influence of THs through TH receptors (TR alpha-1 and TR beta-1) on haematopoiesis in patients with hypo-and hyperthyroidism was analysed.Methods: TR gene expression at the mRNA and protein levels in human CD34(+)-enriched haematopoietic progenitor cells (HPCs) obtained from the peripheral blood of patients with thyroid disorders and healthy volunteers was analysed. The cell populations were also investigated for clonogenic growth of granulocyte macrophage-colony forming units and erythrocyte-burst forming units (BFU-E). The level of apoptosis was determined by annexin V/propidium iodide staining and quantitative RT-PCR.Results: The studies revealed that hypo-and hyperthyroidism modify TR gene expression in HPCs in vivo. TH deficiency resulted in a decrease in total blood counts and clonogenic potential of BFU-E. In contrast, hyperthyroid patients presented increased clonogenic growth and BFU-E number and significantly higher expressions of cell cycle-regulating genes such as those for PCNA and cyclin D1. Finally, an increase in the frequency of apoptotic CD34(+)-enriched HPCs in hypo-and hyperthyroidism with a modulation of apoptosis-related genes was detected.Conclusions: The following conclusions were derived: i) TR expression in human haematopoietic cells depends on TH status, ii) both hypo-and hyperthyroidism significantly influence clonogenicity and induce apoptosis in CD34(+)-enriched HPCs and iii) the molecular mechanism by which THs influence haematopoiesis might provide a basis for designing novel therapeutic interventions in thyroid diseases.