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首页> 外文期刊>Nephrology, dialysis, transplantation: official publication of the European Dialysis and Transplant Association - European Renal Association >Altered folate receptor 2 expression in uraemic patients on haemodialysis: Implications for folate resistance
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Altered folate receptor 2 expression in uraemic patients on haemodialysis: Implications for folate resistance

机译：血液透析患者尿毒症患者叶酸受体2表达的改变：对叶酸抵抗的影响

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Background Folate therapy reduces, but does not normalize homocysteine (Hcy) levels, frequently elevated in chronic kidney disease (CKD). The mechanisms of this folate resistance are unknown. Cellular acquisition of folate is mediated by folate receptors (FRs), whose expression is also modulated by folate status, through an Hcy-dependent regulation mechanism involving heterogeneous nuclear ribonucleoprotein-E1 (hnRNP-E1). Our objective was to evaluate whether an alteration of the FR2 (the form present in nucleated blood cells) expression is present in CKD patients on haemodialysis (HD), and its susceptibility to folate treatment. Methods A population of chronic uraemic patients on HD was enrolled, along with a control group, and studies on FR2 receptor expression and related items were performed in plasma and mononuclear cells from peripheral blood. A subgroup of patients was treated with methyltetrahydrofolate for 1 month.ResultsIn HD, there was a significant reduction in FR2 protein expression compared with controls, not correlated with Hcy concentrations, while its mRNA levels were significantly increased. After folate treatment, there was a significant mRNA decrease, in the absence of significant changes in receptor protein expression. hnRNP-E1 gene and protein expression levels increased pre-treatment, while decreased post-treatment. Conclusions In HD, FR2 expression is altered in peripheral mononuclear cells, since its levels are decreased and are not responsive to variations in Hcy concentration, while the intracellular machinery (receptor mRNA and hnRNP-E1), possibly triggering its regulation, is conserved. These findings provide insight into the mechanisms of folate resistance in uraemia.
机译：背景叶酸治疗可降低但不能使高半胱氨酸（Hcy）水平正常化，而高半胱氨酸（Hcy）水平在慢性肾脏疾病（CKD）中经常升高。抗叶酸的机制尚不清楚。叶酸受体（FRs）介导叶酸的细胞获取，其表达也受叶酸状态的调节，通过涉及异源核糖核蛋白-E1（hnRNP-E1）的Hcy依赖性调节机制。我们的目的是评估在血液透析（HD）后CKD患者中是否存在FR2（有核血细胞中存在的形式）表达的改变及其对叶酸治疗的敏感性。方法招募高龄慢性尿毒症患者和对照组，并在外周血血浆和单核细胞中进行FR2受体表达及相关项目的研究。亚组患者接受了四氢叶酸甲酯治疗1个月。结果在HD中，与对照组相比，FR2蛋白表达显着降低，与Hcy浓度无关，而其mRNA水平却明显升高。叶酸处理后，在受体蛋白表达没有明显变化的情况下，mRNA显着下降。 hnRNP-E1基因和蛋白质表达水平在治疗前增加，而治疗后减少。结论在HD中，FR2表达在外周单核细胞中发生改变，因为它的水平降低并且对Hcy浓度的变化无响应，而保守的可能触发其调节的细胞内机制（受体mRNA和hnRNP-E1）却得以保留。这些发现为尿毒症中叶酸抵抗的机制提供了见识。

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