Molecular insights into the oxygen-sensing pathway and erythropoietin expression regulation in erythropoiesis

Tomc, Jana (avtor), Debeljak, Nataša (avtor)

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 VHL, EGLN, EPAS1 and EPO, 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.

• Jezik: Angleški jezik
• Ključne besede: erythropoiesis, erythropoietin, molecular mechanisms, oxygen-sensing pathway, hypoxia-inducible factor, post-translational modifications, protein interactions, nuclear transport, transcriptional regulation
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.02 - Pregledni znanstveni članek
• Organizacija: MF - Medicinska fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2021
• Št. strani: 16 str.
• Številčenje: Vol. 22, iss. 13, art. 7074
• PID: 20.500.12556/RUL-135740
• UDK: 61
• ISSN pri članku: 1422-0067
• DOI: 10.3390/ijms22137074
• COBISS.SI-ID: 69996547
• Datum objave v RUL: 30.03.2022

Gradivo je del revije

• Naslov: International journal of molecular sciences
• Skrajšan naslov: Int. j. mol. sci.
• Založnik: MDPI
• ISSN: 1422-0067
• COBISS.SI-ID: 2779162

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
• Začetek licenciranja: 01.07.2021

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: eritropoeza, eritropoetin, molekularni mehanizmi

Projekti

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: L3-9279
• Naslov: Genetska osnova eritrocitoz v Sloveniji

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: P1-0390
• Naslov: Funkcijska genomika in biotehnologija za zdravje