Molecular Insights into the Oxygen-Sensing Pathway and Erythropoietin Expression Regulation in Erythropoiesis
Erythropoiesis is regulated by several factors, including the oxygen-sensing pathway as the main regulator of erythropoietin (EPO) synthesis in the kidney. The release of EPO from the kidney and its binding to the EPO receptor (EPOR) on erythrocyte progenitor cells in the bone marrow results in incr...
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MDPI AG
2021-06-01
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author | Jana Tomc Nataša Debeljak |
author_facet | Jana Tomc Nataša Debeljak |
author_sort | Jana Tomc |
collection | DOAJ |
description | Erythropoiesis is regulated by several factors, including the oxygen-sensing pathway as the main regulator of erythropoietin (EPO) synthesis in the kidney. The release of EPO from the kidney and its binding to the EPO receptor (EPOR) on erythrocyte progenitor cells in the bone marrow results in increased erythropoiesis. Any imbalance in these homeostatic mechanisms can lead to dysregulated erythropoiesis and hematological disorders. For example, mutations in genes encoding key players of oxygen-sensing pathway and regulation of EPO production (HIF-EPO pathway), namely <i>VHL</i>, <i>EGLN</i>, <i>EPAS1</i> and <i>EPO</i>, are well known causative factors that contribute to the development of erythrocytosis. We aimed to investigate additional molecular mechanisms involved in the HIF-EPO pathway that correlate with erythropoiesis. To this end, we conducted an extensive literature search and used several in silico tools. We identified genes encoding transcription factors and proteins that control transcriptional activation or repression; genes encoding kinases, deacetylases, methyltransferases, conjugating enzymes, protein ligases, and proteases involved in post-translational modifications; and genes encoding nuclear transport receptors that regulate nuclear transport. All these genes may modulate the stability or activity of HIF2α and its partners in the HIF-EPO pathway, thus affecting EPO synthesis. The theoretical information we provide in this work can be a valuable tool for a better understanding of one of the most important regulatory pathways in the process of erythropoiesis. This knowledge is necessary to discover the causative factors that may contribute to the development of hematological diseases and improve current diagnostic and treatment solutions in this regard. |
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spelling | doaj.art-305943dbd9014f95932edf9591b834d52023-11-22T02:27:10ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012213707410.3390/ijms22137074Molecular Insights into the Oxygen-Sensing Pathway and Erythropoietin Expression Regulation in ErythropoiesisJana Tomc0Nataša Debeljak1Medical Centre for Molecular Biology, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, SloveniaMedical Centre for Molecular Biology, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, SloveniaErythropoiesis is regulated by several factors, including the oxygen-sensing pathway as the main regulator of erythropoietin (EPO) synthesis in the kidney. The release of EPO from the kidney and its binding to the EPO receptor (EPOR) on erythrocyte progenitor cells in the bone marrow results in increased erythropoiesis. Any imbalance in these homeostatic mechanisms can lead to dysregulated erythropoiesis and hematological disorders. For example, mutations in genes encoding key players of oxygen-sensing pathway and regulation of EPO production (HIF-EPO pathway), namely <i>VHL</i>, <i>EGLN</i>, <i>EPAS1</i> and <i>EPO</i>, are well known causative factors that contribute to the development of erythrocytosis. We aimed to investigate additional molecular mechanisms involved in the HIF-EPO pathway that correlate with erythropoiesis. To this end, we conducted an extensive literature search and used several in silico tools. We identified genes encoding transcription factors and proteins that control transcriptional activation or repression; genes encoding kinases, deacetylases, methyltransferases, conjugating enzymes, protein ligases, and proteases involved in post-translational modifications; and genes encoding nuclear transport receptors that regulate nuclear transport. All these genes may modulate the stability or activity of HIF2α and its partners in the HIF-EPO pathway, thus affecting EPO synthesis. The theoretical information we provide in this work can be a valuable tool for a better understanding of one of the most important regulatory pathways in the process of erythropoiesis. This knowledge is necessary to discover the causative factors that may contribute to the development of hematological diseases and improve current diagnostic and treatment solutions in this regard.https://www.mdpi.com/1422-0067/22/13/7074erythropoiesisoxygen-sensing pathwayhypoxia-inducible factorerythropoietinmolecular mechanismspost-translational modifications |
spellingShingle | Jana Tomc Nataša Debeljak Molecular Insights into the Oxygen-Sensing Pathway and Erythropoietin Expression Regulation in Erythropoiesis International Journal of Molecular Sciences erythropoiesis oxygen-sensing pathway hypoxia-inducible factor erythropoietin molecular mechanisms post-translational modifications |
title | Molecular Insights into the Oxygen-Sensing Pathway and Erythropoietin Expression Regulation in Erythropoiesis |
title_full | Molecular Insights into the Oxygen-Sensing Pathway and Erythropoietin Expression Regulation in Erythropoiesis |
title_fullStr | Molecular Insights into the Oxygen-Sensing Pathway and Erythropoietin Expression Regulation in Erythropoiesis |
title_full_unstemmed | Molecular Insights into the Oxygen-Sensing Pathway and Erythropoietin Expression Regulation in Erythropoiesis |
title_short | Molecular Insights into the Oxygen-Sensing Pathway and Erythropoietin Expression Regulation in Erythropoiesis |
title_sort | molecular insights into the oxygen sensing pathway and erythropoietin expression regulation in erythropoiesis |
topic | erythropoiesis oxygen-sensing pathway hypoxia-inducible factor erythropoietin molecular mechanisms post-translational modifications |
url | https://www.mdpi.com/1422-0067/22/13/7074 |
work_keys_str_mv | AT janatomc molecularinsightsintotheoxygensensingpathwayanderythropoietinexpressionregulationinerythropoiesis AT natasadebeljak molecularinsightsintotheoxygensensingpathwayanderythropoietinexpressionregulationinerythropoiesis |