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

Jana Tomc (Avtor), Nataša Debeljak (Avtor)

Povzetek

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 HIF2% 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.

Ključne besede

erythropoiesis;erythropoietin;molecular mechanisms;

Podatki

Jezik:	Angleški jezik
Leto izida:	2021
Tipologija:	1.02 - Pregledni znanstveni članek
Organizacija:	UL MF - Medicinska fakulteta
UDK:	61
COBISS:	69996547
ISSN:	1422-0067
Št. ogledov:	115
Št. prenosov:	47
Ocena:	0 (0 glasov)
Metapodatki:

Ostali podatki

Sekundarni jezik:	Slovenski jezik
Sekundarne ključne besede:	eritropoeza;eritropoetin;molekularni mehanizmi;
Vrsta dela (COBISS):	Članek v reviji
Strani:	str. 1-16
Letnik:	ǂVol. ǂ22
Zvezek:	ǂiss. ǂ13
Čas izdaje:	Jun. 2021
DOI:	10.3390/ijms22137074
ID:	14889983