Hepcidin Regulation and Iron Homeostasis in Chronic Diseases
Summary
Hepcidin is a liver‐derived peptide hormone that serves as the master regulator of systemic iron homeostasis. By binding to the cellular iron exporter ferroportin, hepcidin triggers its internalisation and degradation, thereby restricting iron release from enterocytes, macrophages and hepatocytes. Hepcidin transcription is finely tuned by iron stores via the BMP/SMAD pathway, by erythropoietic demand through erythroferrone, and by inflammatory cytokines—principally interleukin-6—via STAT3 signalling. In chronic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, chronic kidney disease and congestive heart failure, persistent hepcidin overproduction leads to iron sequestration, reduced serum iron and anaemia of chronic disease. Conversely, inadequate hepcidin expression in genetic disorders causes systemic iron overload. Dysregulated hepcidin also contributes to morbidity in chronic infections and malignancy. Recent efforts have identified novel hepcidin modulators, including TMPRSS6 inhibitors and hepcidin agonists or antagonists, offering promising therapeutic strategies to restore iron balance and improve patient outcomes.
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Hepcidin Regulation and Iron Homeostasis in Chronic Diseases publication trend
The graph below shows the total number of articles in hepcidin regulation and iron homeostasis in chronic diseases across all publications each year (not limited to Nature Index journals).
Technical terms
Hepcidin: A peptide hormone produced by hepatocytes that regulates plasma iron by inducing degradation of ferroportin.
Ferroportin: The only known iron exporter on cells such as enterocytes and macrophages, responsible for iron release into plasma.
Anaemia of chronic disease: A normocytic, hypoproliferative anaemia caused by inflammation-driven iron sequestration and suppressed erythropoiesis.
BMP/SMAD pathway: A signalling cascade in which bone morphogenetic proteins modulate hepcidin transcription through SMAD transcription factors.
Transferrin saturation: The fraction of circulating transferrin bound to iron, indicating iron availability for erythropoiesis.
References
- Hepcidin Therapeutics. Pharmaceuticals (2018).
- Hepcidin and ferritin levels as markers of immune cell activation during septic shock, severe COVID-19 and sterile inflammation. Frontiers in Immunology (2023).
- Physiology and Inflammation Driven Pathophysiology of Iron Homeostasis—Mechanistic Insights into Anemia of Inflammation and Its Treatment. Nutrients (2021).
- Renal damage-induced hepcidin accumulation contributes to anemia in angiotensinogen-deficient mice. Clinical Science (2025).
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