RGM Family Involved in the Regulation of Hepcidin Expression in Anemia of Chronic Disease

Abstract

The persistent production of inflammatory cytokines causes anemia of chronic disease (ACD). Playing a central role in the pathophysiology of ACD is hepcidin, a key regulator of iron metabolism. The regulation of hepcidin expression is a complex process intricately controlled by multiple pathways. These include the BMP/SMAD, the HFE–TFR2, and the IL-6/STAT3 pathway, each playing a significant role in this regulation. We detail the critical role of the repulsive guidance molecule (RGM) family, especially hemojuvelin (HJV/RGMc), in regulating hepcidin expression in ACD. HJV functions as a co-receptor for BMPs and positively regulates hepcidin expression. RGMa and RGMb may also regulate hepcidin expression and inflammatory responses. RGM family proteins play essential roles in the interplay between inflammation, iron metabolism, and the immune system, and elucidating them could lead to a better understanding of the pathophysiology of ACD and the development of new therapeutic strategies.