The role of hepcidin, GDF15, and mitoferrin-1 in iron metabolism of polycythemia vera and essential thrombocytosis patients

ALBAYRAK, Canan; Tarkun, Pınar; Atesoglu, Elif Birtas; Eraldemır, Ceyla; Özsoy, Özgür Doğa; Demırsoy, Esra Terzı; Mehtap, Özgür; Gedük, Ayfer

doi:10.3906/sag-1803-13

Cited by 7 publications

(3 citation statements)

References 23 publications

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“…We hypothesised that in PV, where patients develop iron deficiency and have increased erythropoietic drive, hepcidin would be suppressed. However, this was not the case in our PV mouse model, a finding that recapitulates clinical studies that demonstrate hepcidin levels in newly diagnosed PV patients are comparable to healthy controls 62, 63 . Our data suggest that in PV, hepcidin may be upregulated by inflammation.…”

Section: Discussionsupporting

confidence: 81%

Iron homeostasis governs erythroid phenotype in Polycythemia Vera

Bennett

Jackson

Pettikiriarachchi

et al. 2022

Preprint

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Polycythemia Vera (PV) is a myeloproliferative neoplasm driven by activating mutations in JAK2 that result in unrestrained erythrocyte production, increasing patients’ hematocrit and hemoglobin concentration, placing them at risk of life-threatening thrombotic events. Our GWAS of 440 PV cases and 403,351 controls utilising UK Biobank data found that SNPs in HFE known to cause hemochromatosis are highly associated with PV diagnosis, linking iron regulation to PV. Analysis of the FinnGen dataset independently confirmed over-representation of homozygous HFE mutations in PV patients. HFE influences expression of hepcidin, the master regulator of systemic iron homeostasis. Through genetic dissection of PV mouse models, we show that the PV erythroid phenotype is directly linked to hepcidin expression: endogenous hepcidin upregulation alleviates erythroid disease whereas hepcidin ablation worsens it. Further, we demonstrate that in PV, hepcidin is not regulated by expanded erythropoiesis but is likely governed by inflammatory cytokines signalling via GP130 coupled receptors. These findings have important implications for understanding the pathophysiology of PV and offer new therapeutic strategies for this disease.

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Section: Discussionsupporting

confidence: 81%

Iron homeostasis governs erythroid phenotype in Polycythemia Vera

Bennett

Jackson

Pettikiriarachchi

et al. 2022

Preprint

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“…IL6 [1383], CSF3 [1384], SOCS3 [1385], CCL3 [1386], CCL5 [1387], VCAM1 [1388], CCL2 [1387], CXCL12 [1389], KLF10 [1390], FRZB (frizzled related protein) [1391], DUSP1 [1392], IL1B [1393], CCL11 [1394], LMNA (lamin A/C) [1395], WIF1 [1396], IL1RN [1397], IFNG (interferon gamma) [1398], CX3CL1 [1399], BMP2 [1400], CDKN1A [1401], BMP4 [1402], ICAM1 [1403], CD34 [1404], IL33 [1405], FASLG (Fas ligand) [1406], KDM6B [1407], TNF (tumor necrosis factor) [1408], GDF15 [1409], IL2 [1410], INPP4B [1411], FABP4 [1412], CYP2C19 [1413], CXCR4 [1414], DKK2 [1415], PLCB4 [1416], ANXA1 [1417], DUSP6 [1418], CORIN (corin, serine peptidase) [1419], F8 [1420], DDIT4 [1421], IL1R2 [1422], S100A4 [1417], CTSL (cathepsin L) [1423], PTX3 [1424], EFNB1 [1425], MCF2L [1426], FZD4 [1427], CCL26 [1428], PHGDH (phosphoglycerate dehydrogenase) [1429] and FDPS (farnesyl diphosphate synthase) [1430] have been identified as predictive biomarkers of osteoporosis. IL6 [1431], SOCS2 [1432], SOCS3 [1432], DUSP1 [1433], MLF1 [1434], EPHA2 [1435], CD34 [1436], IL33 [1437], GDF15 [1438], IL2 [1439], CD177 [1440], G6PD [1441], NFE2 [1442], PTX3 [1443], IDH1 [1444], MPO (myeloperoxidase) [1445] and KLK1 [1446] might be associated with the pathogenesis of polycythemia. The abnormal expression of IL33 [1447] and TNF (tumor necrosis factor) [1448] contributes to the pneumothorax.…”

Section: Discussionmentioning

confidence: 99%

Identification of key genes and biological pathways in chronic obstructive pulmonary disease using bioinformatics and next generation sequencing data analysis

Vastrad,

Vastrad

2024

Preprint

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Identification of accurate biomarkers is still particularly urgent for improving the poor survival of chronic obstructive pulmonary disease (COPD) patients. In this investigation, we aimed to identity the potential biomarkers in COPD via bioinformatics and next generation sequencing (NGS) data analysis. In this investigation, the differentially expressed genes (DEGs) in COPD were identified using NGS dataset (GSE239897) from Gene Expression Omnibus (GEO) database. Subsequently, gene ontology (GO) and pathway enrichment analysis was conducted to evaluate the underlying molecular mechanisms involved in progression of COPD. Protein-protein interaction (PPI), modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network analysis were performed to determine the hub genes, miRNAs and TFs. The receiver operating characteristic (ROC) analysis was performed to determine the diagnostic value of hub genes. A total of 956 overlapping DEGs (478 up regulated and 478 down regulated genes) were identified in the NGS dataset. DEGs were mainly associated with GO functional terms and pathways in cellular response to stimulus. response to stimulus, immune system and neutrophil degranulation. There were 10 hub genes (MYC, LMNA, VCAM1, MAPK6, DDX3X, SHMT2, PHGDH, S100A9, FKBP5 and RPS6KA2) identified by PPI, modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network analysis. In conclusion, the DEGs, relative GO terms, pathways and hub genes identified in the present investigation might aid in understanding of the molecular mechanisms underlying COPD progression and provide potential molecular targets and biomarkers for COPD.

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“…Hepcidin production could be a defense mechanism against erythroid activity. This hypothesis remains inconclusive as other authors have observed normal hepcidin levels [24]. Third, the physiologically hypoxic intestinal lumen promotes iron absorption independently of hepcidin.…”

Section: Iron Deficiency In Polycythemiamentioning

confidence: 94%

Iron Deficiency and Polycythemia

Randrianarisoa¹,

Ramanandafy²,

Mania³

et al. 2023

Preprint

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Several observations have shown that patients with polycythemia have iron deficiency. Our objectives were to report the prevalence of iron deficiency, to evaluate the diagnostic performance of serum ferritin in polycythemia vera and to describe the mechanisms of this association. This is a retrospective descriptive and analytical study carried out in the internal medicine department of the Henri Mondor Hospital, Aurillac, France. The study involved 114 patients with polycythemia, followed in the department from January 1, 2010 to December 31, 2021. To evaluate the diagnostic performance, the JAK2 mutation was considered as the gold standard of diagnosis. Thirty-three patients had polycythemia vera and 76 patients had secondary polycythemia. The mean age of the patients was 61.79 years (±15.44) with a sex ratio of 4.43. The overall prevalence of iron deficiency was 21.05%. The prevalence was 53% in polycythemia vera group and 1.32% in secondary polycythemia group. The risk of iron deficiency was high in polycythemia vera (OR=115; 95% CI [14.4-918.2], p<0.000). The sensitivity and specificity of serum ferritin were 52.63% and 100% respectively. Assessment of iron deficiency should be part of the initial evaluation of polycythemia. The presence of iron deficiency is specific for polycythemia vera.

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The role of hepcidin, GDF15, and mitoferrin-1 in iron metabolism of polycythemia vera and essential thrombocytosis patients

Cited by 7 publications

References 23 publications

Iron homeostasis governs erythroid phenotype in Polycythemia Vera

Iron homeostasis governs erythroid phenotype in Polycythemia Vera

Identification of key genes and biological pathways in chronic obstructive pulmonary disease using bioinformatics and next generation sequencing data analysis

Iron Deficiency and Polycythemia

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