Crosstalk between oxygen signaling and iron metabolism in renal interstitial fibroblasts

• Published in: Journal of Clinical Biochemistry and Nutrition Vol. 74; no. 3; pp. 179 - 184
• Main Authors: Suzuki, Norio, Iwamura, Yuma, Kato, Koichiro, Ishioka, Hirotaka, Konta, Yusuke, Sato, Koji, Uchida, Nao, Koida, Noa, Sekine, Hiroki, Tanaka, Tetsuhiro, Kumagai, Naonori, Nakai, Taku
• Format: Journal Article
• Language: English
• Published: Japan SOCIETY FOR FREE RADICAL RESEARCH JAPAN 2024; Japan Science and Technology Agency; the Society for Free Radical Research Japan
• Subjects: Erythrocytes; Erythropoiesis; Erythropoietin; Fibroblasts; Growth factors; Hemoglobin; Hypoxia; Iron; iron mobilization; Kidney diseases; Kidneys; Metabolism; Oxidative metabolism; Oxidative stress; Oxygen; Precision medicine; Recycling systems; renal anemia; Renal cortex; renal fibrosis; Review; urinary exfoliated cells; urinary exfoliated cells; renal anemia; renal fibrosis; erythropoietin; iron mobilization
• ISSN: 0912-0009; 1880-5086
• DOI: 10.3164/jcbn.24-8

To maintain the oxygen supply, the production of red blood cells ‍(erythrocytes) is promoted under low-oxygen conditions (hypoxia). Oxygen is carried by hemoglobin in erythrocytes, in which the majority of the essential element iron in the body is contained. Because iron metabolism is strictly controlled in a semi-closed recycling system to protect cells from oxidative stress ‍caused by iron, hypoxia-inducible erythropoiesis is closely coordinated by regulatory systems that mobilize stored iron for hemoglobin synthesis. The erythroid growth factor erythropoietin (EPO) is mainly secreted by interstitial fibroblasts in the renal cortex, which are known as renal EPO-producing (REP) cells, and ‍promotes erythropoiesis and iron mobilization. Intriguingly, EPO production is strongly induced by hypoxia through iron-dependent pathways in REP cells. Here, we summarize recent studies on the network mechanisms linking hypoxia-inducible EPO production, erythropoiesis and iron metabolism. Additionally, we introduce disease mechanisms related to disorders in the network mediated by REP cell functions. Furthermore, we propose future studies regarding the application of renal cells derived from the urine of kidney disease patients to investigate the molecular pathology of chronic kidney disease and develop precise and personalized medicine for kidney disease.