Regulation of hepcidin: Insights from biochemical analyses on human serum samples
Regulation of hepcidin: Insights from biochemical analyses on human serum samples
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DOI：
10.1016/j.bcmd.2007.10.002
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发表时间：
2008-05-01
影响因子：
2.3
通讯作者：
Swinkels, Dorine W.
中科院分区：
文献类型：
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作者：
Kemna, Erwin H. J. M.;Kartikasari, April E. R.;Swinkels, Dorine W.
铁调素调控的知识最先通过体外研究获得。我们的目的是将这一知识转化为人体在vivo situation.So，我们测量血清标记物，如转铁蛋白饱和度（TS），可溶性转铁蛋白受体（sTfR），和C-反应蛋白（CRP）平行铁调素和前铁调素在铁代谢紊乱患者和对照组。为了探讨sTfR在铁调素调控中的作用，我们研究了sTfR对HepG 2细胞铁调素表达的影响，结果发现sTfR与红细胞生成活性密切相关，强烈干扰铁调素对铁储存的调控。HepG 2表达结果显示铁调素和sTfR之间的负相关。炎症与铁调素水平的增加密切相关，而与铁储存和红细胞生成活性状态无关。相比之下，prohepcidin未能与任何其他parameter.In结论，这些研究证实，以前的结论的基础上，在体外研究hepicidin调节也可能适用于人类患者。这是强调了一个简单的算法，基于参数反映的主要调节途径，准确地预测实际测量的hepcidin水平。需要进一步的研究来验证这种预测算法与实际测量的铁调素水平在临床诊断中的组合效用。(C)2007爱思唯尔公司All rights reserved.
Knowledge of hepcidin regulation is foremost gained by in vitro studies. We aimed to translate this knowledge into the human in vivo situation.Therefore, we measured serum markers as transferrin saturation (TS), soluble transferrin receptor (sTfR), and C-reactive protein (CRP) in parallel with hepcidin and prohepcidin in patients with iron metabolism disorders and controls. To assess sTfR as erythropoietic activity-associated factor in hepcidin regulation, we studied its influence on hepcidin expression in HepG2 cells.Results showed that sTfR highly associates with erythropoietic activity that strongly interfered with the iron store regulation of hepcidin. HepG2 expression results display an inverse association between hepcidin and sTfR. Inflammation was strongly related to increased hepcidin levels regardless of the iron store and erythropoietic activity status. In contrast, prohepcidin failed to correlate to any other parameter.In conclusion, these studies verify that previous conclusions based on in vitro studies on hepicidin regulation are also likely to apply to human patients. This is underscored by a simple algorithm, based on parameters reflecting the main regulating pathways, that accurately predict the actual measured hepcidin levels. Future studies are needed to validate the combined utility of this predictive algorithm together with actual measured hepcidin levels in clinical diagnosis. (C) 2007 Elsevier Inc. All rights reserved.