Jaratsittisin Janejira, Sornjai Wannapa, Svasti Saovaros, Fucharoen Suthat, Roytrakul Sittiruk, Smith Duncan R
a Institute of Molecular Biosciences , Mahidol University , Salaya , Thailand.
b National Science and Technology Development Agency , National Center for Genetic Engineering and Biotechnology (BIOTEC) , Pathum Thani , Thailand.
Hematology. 2018 Aug;23(7):423-428. doi: 10.1080/10245332.2017.1405571. Epub 2017 Nov 21.
The inherited genetic disorder beta0-thalassemia/Hb E disease is associated with the over-suppression of the master regulator of iron homeostasis, the peptide hormone hepcidin. How developing erythroid cells mediate the suppression of hepcidin remains controversial, although a number of inhibitors have been proposed.
To investigate the ability of erythroid cells to suppress hepcidin expression in liver cells, conditioned media from the culture of in vitro differentiating erythroblasts (from normal controls and beta0-thalassemia/Hb E patients) was used to treat HepG2 cells, and the effects on hepcidin expression were assayed by real-time quantitative PCR and confocal microscopy.
Early activation followed by later suppression of hepcidin expression was seen posttreatment. Markedly, however, no significant differences were observed between suppression of hepcidin as mediated by media from the culture of erythroblasts from normal controls and beta0-thalassemia/Hb E patients Discussion: Previous studies investigating the suppression of hepcidin expression in beta0-thalassemia/Hb E disease have used patient-derived serum samples, which are complex fluids with contributions from multiple cell types. This study has developed a simple in vitro system that allows investigation of how a single cell type mediates hepcidin expression. The results support proposals that over-suppression of hepcidin seen in beta-thalassemia/Hb E patients is a consequence of the increased mass of erythropoiesis and not defects in the signaling process per se.
The in vitro cell system developed here allows further investigation into the processes mediating erythroid cell suppression of liver hepcidin expression in both normal and pathological states.
遗传性基因疾病β0地中海贫血/Hb E病与铁稳态的主要调节因子——肽激素铁调素的过度抑制有关。尽管已经提出了多种抑制剂，但发育中的红系细胞如何介导铁调素的抑制仍存在争议。
为了研究红系细胞抑制肝细胞中铁调素表达的能力，使用体外分化的成红细胞（来自正常对照和β0地中海贫血/Hb E患者）培养的条件培养基处理HepG2细胞，并通过实时定量PCR和共聚焦显微镜检测对铁调素表达的影响。
处理后可见铁调素表达先激活后抑制。然而，值得注意的是，正常对照和成红细胞培养物的培养基介导的铁调素抑制与β0地中海贫血/Hb E患者的培养基介导的铁调素抑制之间未观察到显著差异。讨论：先前研究β0地中海贫血/Hb E病中铁调素表达抑制的研究使用了患者来源的血清样本，这些样本是复杂的液体，由多种细胞类型组成。本研究开发了一种简单的体外系统，可用于研究单一细胞类型如何介导铁调素表达。结果支持了以下观点，即β地中海贫血/Hb E患者中所见的铁调素过度抑制是红细胞生成增加的结果，而非信号传导过程本身存在缺陷。
此处开发的体外细胞系统允许进一步研究在正常和病理状态下介导红系细胞抑制肝脏铁调素表达的过程。
