Impact of BMP-SMAD and JAK-STAT Signaling Pathways on Hepcidin Protein Expression and Iron Overloading in β-Thalassemia: A Review

Aarti Saini, Kanchan Bhardwaj, Rajinder Kaur

Abstract: Thalassemia represents an inherited blood disorder with a recessive genetic pattern that causes problems with hemoglobin production and leads to dysfunctional red blood cells and ongoing anemia. β-thalassemia patients show reduced levels of hepcidin hormone which controls iron homeostasis thereby leading to iron regulation problems. When hepcidin levels fall depleted, it raises the amount of iron that the intestines absorb while macrophages release too much iron which results in excessive iron accumulation throughout the body. β-thalassemia patients need blood transfusions face increased risks of endocrine disorders together with hepatic damage and heart complications owing to continued iron accumulation. Through its mechanism the protein hepcidin breaks down ferroportin which controls cell-based iron release thus restricting iron access from diet and stored reserves. The deregulation of hepcidin results in an abnormal iron imbalance where patients experience simultaneous iron deficiency anemia along with toxic iron buildup. Multiple signaling pathways control hepcidin regulation which includes bone morphogenetic protein/ small mothers against decapentaplegic (BMP/SMAD) as well as the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway together with erythroferrone (ERFE) and growth differentiation factor 15 (GDF15). The treatment strategies for restoring iron equilibrium combine hepcidin agonists with BMP pathway activators alongside ERFE inhibitor administration to promote hepcidin production while stopping its suppression. The review establishes how hepcidin-associated signaling interacts with iron regulation within β-thalassemia while examining its importance for medical treatment approaches.

Keywords: β-thalassemia, erythropoiesis, hepcidin, iron overloading, JAK/STAT, BMP/SMAD

How to Cite?: Aarti Saini, Kanchan Bhardwaj, Rajinder Kaur, "Impact of BMP-SMAD and JAK-STAT Signaling Pathways on Hepcidin Protein Expression and Iron Overloading in β-Thalassemia: A Review", Volume 14 Issue 5, May 2025, International Journal of Science and Research (IJSR), Pages: 10-14, https://www.ijsr.net/getabstract.php?paperid=SR25428204245, DOI: https://dx.doi.org/10.21275/SR25428204245