title: Altered folate receptor 2 expression in uraemic patients on haemodialysis: implications for folate resistance.
abstract: 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.
  
  
  RESULTS
  In 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.
authors: First Division of Nephrology, Department of Cardio-thoracic and Respiratory Sciences, Second University of Naples, School of Medicine, Naples, Italy. alessandra.perna@unina2.it
authors: Alessandra F
authors: AF
authors: Perna
authors: Diana
authors: D
authors: Lanza
authors: Immacolata
authors: I
authors: Sepe
authors: Giovanni
authors: G
authors: Conzo
authors: Lucia
authors: L
authors: Altucci
authors: Diego
authors: D
authors: Ingrosso
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D016022:Case-Control Studies; D002908:Chronic Disease; D004268:DNA-Binding Proteins; D004351:Drug Resistance; D005260:Female; D005434:Flow Cytometry; D058976:Folate Receptor 2 / Q000235:genetics / Q000378:metabolism*; D005492:Folic Acid / Q000008:administration & dosage*; D005500:Follow-Up Studies; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins; D060888:Real-Time Polymerase Chain Reaction; D006435:Renal Dialysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014511:Uremia / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D004268:DNA-Binding Proteins; D058976:Folate Receptor 2; D034441:Heterogeneous-Nuclear Ribonucleoproteins; C094604:PCBP1 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D005492:Folic Acid
keywords: folate receptors; folates; haemodialysis; heterogeneous nuclear ribonucleoprotein-E1; homocysteine