Host: The Japanese Society of Toxicology
Name : The 49th Annual Meeting of the Japanese Society of Toxicology
Date : June 30, 2022 - July 02, 2022
Erythropoietin (EPO) is not only essential for the production of red blood cells, but also has a variety of functions including cytoprotection. EPO receptors (EPOR) are expressed not only on hematopoietic stem cells in the bone marrow but also on various other cells, and the signaling pathways from EPORs through JAK2/STAT5, MAPK, and PI3K/AKT are known. Human hepatocarcinoma-derived HepG2 cells are EPO-producing cells and express EPOR, and the effects of EPOR-mediated EPO may affect EPO production, but the details are not clear. The purpose of this study was to analyze the signaling pathway by which recombinant human (rh) EPO administration affects EPO production using HepG2 cells.
The mRNA expression of EPO was significantly increased by rhEPO treatment, suggesting that EPO production was increased. siEPOR treatment abolished the effect of rhEPO treatment, suggesting that rhEPO affects EPO production via EPOR. JAK2/ STAT5 signaling pathway increases sirtuin1 activity via nicotinamide phosphoribosyltransferase and has an inhibitory effect on hypoxia-inducible factor (HIF), a regulator of EPO production, while the PI3K / Akt signaling pathway. Simultaneous treatment with STAT5 inhibitor and rhEPO significantly increased the mRNA expression of EPO. These results suggest that rhEPO promotes EPOR-mediated EPO production and inhibited by the JAK2 / STAT5 pathway, which may prevent excessive EPO production. HepG2 cells were considered to have feedback regulation by the EPO produced by themselves.
