Introduction

• Hepcidin (Hepc) is a crucial hormone discovered in the 2000s.
• Produced in the liver, it manages iron intake, storage, and movement throughout the body.

Molecular Characteristics and Biosynthesis

• Hepcidin is encoded by the HAMP gene.
• Produced primarily in hepatocytes.
• Synthesized as a preprohormone and processed into a 25-amino acid mature peptide.
• Belongs to the antimicrobial peptide family.
• Structural highlights:
• Compact, disulfide-stabilized structure
• High structural stability
• Ability to interact with multiple cellular receptors

Regulatory Mechanisms

• Production influenced by multiple physiological signals:
• Iron body stores
• Inflammatory responses
• Erythropoietic activity
• Oxygen availability
• Metabolic state
• Key regulatory pathways:
• Bone morphogenetic protein (BMP) signalling
• STAT3 activation
• Hemojuvelin interactions
• Transferrin saturation monitoring

Iron Metabolism Regulation

• Primary mechanism of action involves interaction with ferroportin (the sole known cellular iron exporter):
• Binds to ferroportin on iron-exporting cells
• Triggers internalization and degradation of ferroportin
• Prevents iron release from:
• Intestinal absorptive cells
• Macrophages
• Hepatocytes
• Placental cells
• Ensures precise regulation of systemic iron distribution, preventing iron deficiency and overload.

Immune Defence and Inflammatory Response

• Plays a crucial role in immune system functioning:
• Antimicrobial Properties:
• Direct antimicrobial activity against pathogens
• Restricts iron availability during infections
• Supports innate immune defence mechanisms
• Contributes to host defence strategy
• Inflammatory Modulation:
• Increases during inflammatory conditions
• Acts as an acute-phase protein
• Mediates host response to infections
• Helps prevent pathogen proliferation by limiting iron access
• Disease Associations:
• Anemia of chronic disease
• Hereditary hemochromatosis
• Iron-refractory iron deficiency anemia
• Chronic kidney disease
• Certain inflammatory disorders

Emerging Therapeutic Strategies

• Cutting-edge research explores hepcidin's potential in:
• Developing targeted iron metabolism treatments
• Creating novel antimicrobial therapies
• Managing chronic inflammatory conditions
• Designing personalized metabolic interventions
• Potential therapeutic approaches include:
• Hepcidin mimetics
• Hepcidin inhibitors
• Precision medicine targeting iron metabolism
• Modulating inflammatory responses