Transferrin Receptor
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QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Khaled Abou seif ◽  
Hussien Sayed Hussien ◽  
Shaimaa Abdelmegied ◽  
Marwa Abdulhady

Abstract: Background Diagnosis of iron deficiency is traditionally based on ferritin and other iron parameters becomes difficult in end stage renal disease patients due to the inflammatory condition which affects these markers and masks the iron deficiency. Serum soluble transferrin receptor (sTfR) is able to be a reliable indicator for assessing iron status, as it is not affected by inflammatory procedures. Aim To evaluate the usefulness of serum soluble transferrin receptors in iron deficiency anemia detection in comparison to the classic markers of iron status in prevalent hemodialysis patients. Methods This case-control study assessed sTfR in 80 prevalent ESRD patients on regular hemodialysis in 2 groups. Group A (N = 40): CRP >10 and group B (N = 40):CRP <10 and apparently healthy 8 control subjects. Results The cut of value of STFRs in hemodialysis patients was 12.5 mg\l. The prevalence of STFRs in patients with CRP<10 was 85%, while in patients with CRP>10 was 92.5% (P-value 0.288). STFRs have high sensitivity 88.75, specificity 100, PPV100% and NPV 47.1%. The hemodialysis patients who have elevated STFRs have risk 1.22 times to have iron deficiency anemia if CRP <10 (odds ratio: 1.22) and 3.14 times if CRP>10 (odds ratio: 3.14). There was significant difference on comparing patients with CRP<10, CRP>10 and control as regard Hb and STFR with P-value 0.0001 and 0.0001 respectively. Post Hoc analysis showed significant difference in both between the patients with CRP<10 and control also in patients with CRP>10 and control (p value <0.0001). while on comparing patients with CRP<10 with patients with CRP>10 there was significant difference in STFRs p value 0.0001 despite no significant difference in hemoglobin (p value 0.642) and classic marker of iron deficiency (s.iron, TIBC, TSAT) with p value 0.701,0.192,0.382 respectively. Serum STFRs was negatively correlated with s.iron and Kt\v (r -0.372, P-value 0.018) and (r-0.416, p value 0.008) respectively in patients with CRP <10. Conclusion Serum soluble transferrin receptor is highly sensitive and specific marker for iron deficiency in hemodialysis patients especially in patients with high CRP level.

2021 ◽  
Vol 18 (1) ◽  
Claire Simonneau ◽  
Martina Duschmalé ◽  
Alina Gavrilov ◽  
Nathalie Brandenberg ◽  
Sylke Hoehnel ◽  

Abstract Background The pathways that control protein transport across the blood–brain barrier (BBB) remain poorly characterized. Despite great advances in recapitulating the human BBB in vitro, current models are not suitable for systematic analysis of the molecular mechanisms of antibody transport. The gaps in our mechanistic understanding of antibody transcytosis hinder new therapeutic delivery strategy development. Methods We applied a novel bioengineering approach to generate human BBB organoids by the self-assembly of astrocytes, pericytes and brain endothelial cells with unprecedented throughput and reproducibility using micro patterned hydrogels. We designed a semi-automated and scalable imaging assay to measure receptor-mediated transcytosis of antibodies. Finally, we developed a workflow to use CRISPR/Cas9 gene editing in BBB organoid arrays to knock out regulators of endocytosis specifically in brain endothelial cells in order to dissect the molecular mechanisms of receptor-mediated transcytosis. Results BBB organoid arrays allowed the simultaneous growth of more than 3000 homogenous organoids per individual experiment in a highly reproducible manner. BBB organoid arrays showed low permeability to macromolecules and prevented transport of human non-targeting antibodies. In contrast, a monovalent antibody targeting the human transferrin receptor underwent dose- and time-dependent transcytosis in organoids. Using CRISPR/Cas9 gene editing in BBB organoid arrays, we showed that clathrin, but not caveolin, is required for transferrin receptor-dependent transcytosis. Conclusions Human BBB organoid arrays are a robust high-throughput platform that can be used to discover new mechanisms of receptor-mediated antibody transcytosis. The implementation of this platform during early stages of drug discovery can accelerate the development of new brain delivery technologies.

2021 ◽  
Haibo Zhao ◽  
Bhaba K Das ◽  
Lei Wang ◽  
Toshifumi Fujiwara ◽  
Jian Zhou ◽  

Increased intracellular iron spurs mitochondrial biogenesis and respiration to satisfy high-energy demand during osteoclast differentiation and bone-resorbing activities. Transferrin receptor 1 (TFR1) mediates cellular iron uptake through endocytosis of iron-loaded transferrin and its expression increases during osteoclast differentiation. Nonetheless, the precise functions of TFR1 and TFR1-mediated iron uptake in osteoclast biology and skeletal homeostasis remain incompletely understood. To investigate the role of TFR1 in osteoclast lineage cells, we conditionally deleted Tfr1 gene in myeloid precursors or mature osteoclasts by crossing Tfr1-floxed mice with LysM-Cre and Ctsk-Cre mice, respectively. Skeletal phenotyping by μCT and histology unveiled that loss of Tfr1 in osteoclast progenitor cells resulted in a three-fold increase in trabecular bone mass in the long bones of 10-week old female but not male mice. Although high trabecular bone volume in long bones was seen in both male and female mice with deletion of Tfr1 in mature osteoclasts, this phenotype was more pronounced in female knockout mice. Mechanistically, disruption of Tfr1 expression attenuated mitochondrial metabolism and cytoskeletal organization in mature osteoclasts, leading to decreased bone resorption with no impact on osteoclastogenesis. These results indicate that Tfr1-mediated iron uptake is specifically required for osteoclast function and is indispensable for bone remodeling.

Deepika Gujjarlapaudi ◽  
Namburu Veeraiah ◽  
Syed Hassan Naveed ◽  
Duvvuru Nageswara Reddy

Background: Anemia is most common complication in IBD (inflammatory bowel disease). The aim of the study was to assess the sTfR-F (soluble transferrin receptor-ferritin) index as early marker of IDA (iron deficiency anaemia) in IBD.Methods: Retrospective cross sectional study has 480 cases of IBD (group I ) with controls 220 (group II), CBP, serum hsCRP, serum iron, TIBC (total iron binding capacity), sTfR, ferritin, fecal calprotectin, vitamin B12, folic acid were assessed.Results: In study I, group I was compared with group II showed (66.5%) patients had active disease and in that 65.0% of UC, 32.1% of CD and 2.9% others colitis had anemia. In study II, subgroup I 56.4% had IDA subgroup II 7.3% had ferritin between 30-100 ng/ml combi subgroup III 23.3% had ferritin>100 ng/ml (ACD, anaemia of chronic disease) subgroup IV 5.6% had vitamin B12 and folic acid deficiency excluding sTfR-F analysis. In study III, subdivided to identify IDA with sTfR-F index as group A 60.8% had sTfR-F index>2, group B 32.6% had sTfR-F index=1-2 and group C 3 (6.2%) had sTfR-F index<1. Intially diagnosed IDA was 56.4%, in addition with group A, IDA has increased by 66.5%. In study IV, in IDA, sensitivity of sTfR-F index was100%, sTfR 89% and SF 85%. Specificity of sTfR and sTfR-F index were 80.60% and SF has low specificity 73.90%. In study V, a statistical significance was seen more in female than male and in children than in adults with sTfR-F index in IDA.Conclusions: sTfR-F index as an early diagnostic marker, in differentiating IDA, ACD and combi in IBD patients.

2021 ◽  
Vol 22 (16) ◽  
pp. 8923
Nan Zhang ◽  
Tao Bing ◽  
Luyao Shen ◽  
Le Feng ◽  
Xiangjun Liu ◽  

General cancer-targeted ligands that can deliver drugs to cells have been given considerable attention. In this paper, a high-affinity DNA aptamer (HG1) generally binding to human tumor cells was evolved by cell-SELEX, and was further optimized to have 35 deoxynucleotides (HG1-9). Aptamer HG1-9 could be taken up by live cells, and its target protein on a cell was identified to be human transferrin receptor (TfR). As a man-made ligand of TfR, aptamer HG1-9 was demonstrated to bind at the same site of human TfR as transferrin with comparable binding affinity, and was proved to cross the epithelium barrier through transferrin receptor-mediated transcytosis. These results suggest that aptamer HG1-9 holds potential as a promising ligand to develop general cancer-targeted diagnostics and therapeutics.

2021 ◽  
Vol 22 (15) ◽  
pp. 8209
Betty Berezovsky ◽  
Martin Báječný ◽  
Jana Frýdlová ◽  
Iuliia Gurieva ◽  
Daniel Wayne Rogalsky ◽  

Erythropoietin (EPO) downregulates hepcidin expression to increase the availability of iron; the downregulation of hepcidin is mediated by erythroferrone (ERFE) secreted by erythroblasts. Erythroblasts also express transferrin receptor 2 (TFR2); however, the possible role of TFR2 in hepcidin downregulation is unclear. The purpose of the study was to correlate liver expression of hepcidin with the expression of ERFE and TFR2 in murine bone marrow and spleen at 4, 16, 24, 48, 72 and 96 h following administration of a single dose of EPO. Splenic Fam132b expression increased 4 h after EPO injection; liver hepcidin mRNA was decreased at 16 h. In the spleen, expression of TFR2 and transferrin receptor (TFR1) proteins increased by an order of magnitude at 48 and 72 h after EPO treatment. The EPO-induced increase in splenic TFR2 and TFR1 was associated with an increase in the number of Tfr2- and Tfr1-expressing erythroblasts. Plasma exosomes prepared from EPO-treated mice displayed increased amount of TFR1 protein; however, no exosomal TFR2 was detected. Overall, the results confirm the importance of ERFE in stress erythropoiesis, support the role of TFR2 in erythroid cell development, and highlight possible differences in the removal of TFR2 and TFR1 from erythroid cell membranes.

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2600
Tao Thi Tran ◽  
Madhawa Gunathilake ◽  
Jeonghee Lee ◽  
Il Ju Choi ◽  
Young-Il Kim ◽  

Background: A positive association between a high iron intake and colorectal cancer has been identified; however, the effect of dietary iron on gastric cancer (GC) remains unclear. Here, we investigate whether dietary iron is related to GC risk and whether the transferrin receptor (TFRC) rs9846149 polymorphism modifies this association. Methods: A case–control study was designed to assess this association among 374 GC patients and 754 healthy controls. A self-administered questionnaire was used to collect information on demographics, medical history and lifestyle. Dietary iron intake was assessed using a semi-quantitative food frequency questionnaire. TFRC rs9846149 was genetically analyzed using the Affymetrix Axiom Exom 319 Array platform. Results: A higher total dietary iron was significantly associated with decreased GC risk [OR = 0.65 (0.45–0.94), p for trend = 0.018]. A similar association was observed with nonheme iron [OR = 0.64 (0.44–0.92), p for trend = 0.018]. Individuals with a major allele of TFRC rs9846149 (CC/GC) and higher intake of total iron had a significantly lower GC risk than those with a lower intake [OR = 0.60 (0.41–0.88), p interaction = 0.035]. Conclusion: Our findings show the protective effects of total dietary iron, especially nonheme iron, against GC risk, and this association can be modified by TFRC rs9846149.

2021 ◽  
Vol 12 (1) ◽  
Krzysztof Kucharz ◽  
Kasper Kristensen ◽  
Kasper Bendix Johnsen ◽  
Mette Aagaard Lund ◽  
Micael Lønstrup ◽  

AbstractEffective treatments of neurodegenerative diseases require drugs to be actively transported across the blood-brain barrier (BBB). However, nanoparticle drug carriers explored for this purpose show negligible brain uptake, and the lack of basic understanding of nanoparticle-BBB interactions underlies many translational failures. Here, using two-photon microscopy in mice, we characterize the receptor-mediated transcytosis of nanoparticles at all steps of delivery to the brain in vivo. We show that transferrin receptor-targeted liposome nanoparticles are sequestered by the endothelium at capillaries and venules, but not at arterioles. The nanoparticles move unobstructed within endothelium, but transcytosis-mediated brain entry occurs mainly at post-capillary venules, and is negligible in capillaries. The vascular location of nanoparticle brain entry corresponds to the presence of perivascular space, which facilitates nanoparticle movement after transcytosis. Thus, post-capillary venules are the point-of-least resistance at the BBB, and compared to capillaries, provide a more feasible route for nanoparticle drug carriers into the brain.

2021 ◽  
Vol 32 (4) ◽  
pp. 491-496
Prihartini Widiyanti ◽  
Hartmut Kuehn ◽  
Soetjipto Soetjipto

Abstract Objectives Iron is essential for cell growth, differentiation, electron transfer, and oxygen transport. Hyperoxia may increase the turnover of bone matrix components with a net effect of accelerated bone growth. Although hyperoxia was claimed could increase osteoblast activity, but expression level in possible genes which play role in proliferation is still unclear. This research aims to prove the differences of expression level of transferrin receptor gene and iron regulated transporter and other genes of 7F2 under 24 h normoxia, 24 h hyperoxia, and 48 h hyperoxia and the effect of hyperoxia by using osteoblast cell culture 7F2. Methods Reverse transcriptase, real time Polymerase Chain Reaction (PCR), and microarray is used to qualitatively detect gene expression. The computer softwares such as National Center for Biotechnology Information (NCBI) data base, Software Affymetrix, DNA Strider program, Genomatix – DiAlign program, Oligo 5.0 program (Software primer design) from Wojciech & Piotr Rychlik, and Genetyx-Mac version 8.0 have been used to analyze the PCR result. Results Under 24 h hyperoxia, there were 3,884 copies of transferrin receptor mRNA per 1,000,000 copies of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA. After 24 h hyperoxia, 8,325 copies of transferrin receptor mRNA per 1,000,000 GAPDH mRNA copies were found showing 2.1-fold up regulation. After 48 h hyperoxia, there was no significant increase at the level of expression of transferrin receptor mRNA, 8,079 mRNA copies per 1,000,000 copies of mRNA were found (2.0-fold up regulation compared with 24 h normoxia). Conclusions It can be concluded that hyperoxia might have an effect on upregulating the expression of some osteoblast genes which might have an impact on osteoblast activity.

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2160
Malaine Morais Alves Machado ◽  
Mirella de Paiva Lopes ◽  
Raquel Machado Schincaglia ◽  
Paulo Sérgio Sucasas da Costa ◽  
Alexandre Siqueira Guedes Coelho ◽  

Fortification with multiple micronutrient powder has been proposed as a public health intervention able to reduce micronutrient deficiencies in children. Our objective was to compare the effectiveness of fortification with multiple micronutrient powder with drug supplementation in the prevention and treatment of iron deficiency and anaemia. This was a cluster trial with anemic and non-anaemic children between six and 42 months old, in randomization data. Non anaemic children received fortification with multiple micronutrient powder or standard drug supplementation of ferrous sulfate associated with folic acid in a prevention dose. Anaemic children who were randomized to receive multiple micronutrient powder also received the recommended iron complementation for anaemia treatment. A total of 162 children were evaluated. The prevalence of anaemia decreased from 13.58 to 1.85%. Iron deficiency decreased from 21.74% to 7.89% (by serum ferritin) and iron deficiency decreased from 66.81 to 38.27% (by soluble transferrin receptor). No difference was identified between interventions for hemoglobin (p = 0.142), serum ferritin (p = 0.288), and soluble transferrin receptor (p = 0.156). Fortification with multiple micronutrient powder was effective in preventing iron deficiency and anaemia in children aged six to 48 months. In anaemic children; it was necessary to supplement the dose of multiple micronutrient powder with ferrous sulfate.

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