Frýdlová Jana, Rychtarčíková Zuzana, Gurieva Iuliia, Vokurka Martin, Truksa Jaroslav, Krijt Jan
Institute of Pathological Physiology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
Laboratory of Tumour Resistance, Institute of Biotechnology, BIOCEV Research Center, Czech Academy of Sciences, Vestec, Czech Republic.
PLoS One. 2017 Oct 26;12(10):e0186844. doi: 10.1371/journal.pone.0186844. eCollection 2017.
Tmprss6-mutated mask mice display iron deficiency anemia and high expression of hepcidin. The aim of the study was to determine the effect of erythropoietin administration on proteins participating in the control of iron homeostasis in the liver and spleen in C57BL/6 and mask mice. Administration of erythropoietin for four days at 50 IU/mouse/day increased hemoglobin and hematocrit in C57BL/6 mice, no such increase was seen in mask mice. Erythropoietin administration decreased hepcidin expression in C57BL/6 mice, but not in mask mice. Erythropoietin treatment significantly increased the spleen size in both C57BL/6 and mask mice. Furthermore, erythropoietin administration increased splenic Fam132b, Fam132a and Tfr2 mRNA content. At the protein level, erythropoietin increased the amount of splenic erythroferrone and transferrin receptor 2 both in C57BL/6 and mask mice. Splenic ferroportin content was decreased in erythropoietin-treated mask mice in comparison with erythropoietin-treated C57BL/6 mice. In mask mice, the amount of liver hemojuvelin was decreased in comparison with C57BL/6 mice. The pattern of hemojuvelin cleavage was different between C57BL/6 and mask mice: In both groups, a main hemojuvelin band was detected at approximately 52 kDa; in C57BL/6 mice, a minor cleaved band was seen at 47 kDa. In mask mice, the 47 kDa band was absent, but additional minor bands were detected at approximately 45 kDa and 48 kDa. The results provide support for the interaction between TMPRSS6 and hemojuvelin in vivo; they also suggest that hemojuvelin could be cleaved by another as yet unknown protease in the absence of functional TMPRSS6. The lack of effect of erythropoietin on hepcidin expression in mask mice can not be explained by changes in erythroferrone synthesis, as splenic erythroferrone content increased after erythropoietin administration in both C57BL/6 and mask mice.
跨膜丝氨酸蛋白酶6（Tmprss6）突变的面具小鼠表现出缺铁性贫血和铁调素的高表达。本研究的目的是确定给予促红细胞生成素对C57BL/6小鼠和面具小鼠肝脏及脾脏中参与铁稳态调控的蛋白质的影响。以50 IU/小鼠/天的剂量给予促红细胞生成素4天，可使C57BL/6小鼠的血红蛋白和血细胞比容增加，而面具小鼠未出现这种增加。给予促红细胞生成素可降低C57BL/6小鼠的铁调素表达，但对面具小鼠无此作用。促红细胞生成素治疗显著增加了C57BL/6小鼠和面具小鼠的脾脏大小。此外，给予促红细胞生成素增加了脾脏中Fam132b、Fam132a和Tfr2的mRNA含量。在蛋白质水平上，促红细胞生成素增加了C57BL/6小鼠和面具小鼠脾脏中的红细胞铁调素和转铁蛋白受体2的量。与促红细胞生成素治疗的C57BL/6小鼠相比，促红细胞生成素治疗的面具小鼠脾脏中的铁转运蛋白含量降低。与C57BL/6小鼠相比，面具小鼠肝脏中的血色素沉着蛋白量减少。C57BL/6小鼠和面具小鼠血色素沉着蛋白的裂解模式不同：在两组中，均在约52 kDa处检测到一条主要的血色素沉着蛋白条带；在C57BL/6小鼠中，在47 kDa处可见一条较小的裂解条带。在面具小鼠中，47 kDa条带缺失，但在约45 kDa和48 kDa处检测到额外的较小条带。这些结果为体内TMPRSS6与血色素沉着蛋白之间的相互作用提供了支持；它们还表明，在缺乏功能性TMPRSS6的情况下，血色素沉着蛋白可能被另一种未知的蛋白酶裂解。促红细胞生成素对面具小鼠铁调素表达缺乏影响，不能用红细胞铁调素合成的变化来解释，因为在C57BL/6小鼠和面具小鼠中给予促红细胞生成素后，脾脏中的红细胞铁调素含量均增加。
