RGM Family Involved in the Regulation of Hepcidin Expression in Anemia of Chronic Disease
Abstract
:1. Introduction
2. History of Hepcidin Discovery
3. Role of Hepcidin in Iron Metabolism
4. Mechanism of Regulation of Hepcidin Production by Iron Levels in the Body
5. Role of Hepcidin in ACD
6. Multifaceted Control of Hepcidin Expression through HJV and Associated Molecules
- a
- Membrane-bound HJV activates hepcidin transcription through the BMP/Smad pathway
- b
- Soluble HJV suppresses hepcidin transcription via the BMP/SMAD pathway
- c
- Regulation of hepcidin expression by Neogenin
- d
- Regulation of hepcidin expression by the HFE–TFR2 pathway
- e
- Regulation of hepcidin expression by IL-6/STAT3 pathway in ACD
7. RGM Family Involved in Hepcidin Synthesis in ACD
- a
- Hemojuvelin (HJV/RGMc)
- b
- RGMa
- c
- RGMb
8. Hepcidin Regulation via the RGM Family in Acute Disease
9. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Characteristics | RGMa | RGMb (Dragon) | RGMc (HJV) |
---|---|---|---|
Alias | - | Dragon | Hemojuvelin, HFE2 |
Main expression site | Central nervous system [19,85,86,87,88,89,90] | Lung stroma, lung epithelium, neural tissue, macrophages, bronchial epithelial cells, activated eosinophils [91,92] | Liver and skeletal muscle [14,67,68,74,75,93] |
Role in hepcidin synthesis | Promotes hepcidin transcription by acting as a co-receptor for BMPs in HuH7 cells, hepatocarcinoma cell line [78] | May promote hepcidin expression through SMAD1 activation via the BMP signaling pathway, but its direct role in hepcidin regulation remains unclear [94] | Positively regulates hepcidin expression as a co-receptor for BMPs [14,16,17] |
Involvement in BMP/SMAD pathway | Acts as a co-receptor for BMPs, promoting BMP/SMAD signaling [15] | Functions as a BMP co-receptor, binding directly to BMP2 and BMP4, and to BMP type I and II receptors. Effects on BMP signaling may be cell-type specific: it inhibits BMP signaling in C2C12 myoblasts, but promotes signaling in others [94,95,96] | Enhances BMP signaling as a co-receptor, crucial for BMP/SMAD pathway activation [14,16,17] |
Involvement in IL6/STAT3 pathway | No direct involvement reported in the paper | Negatively regulates IL-6 expression, but no direct involvement in IL6/STAT3 pathway reported [97] | No direct involvement reported, but essential for IL-6-induced hepcidin expression [98] |
Association with inflammation | Involved in neuroinflammatory diseases [87,88,90] | Regulates inflammatory responses, negatively regulates IL-6 expression [97] | Essential for hepcidin induction during inflammation [14,98,99] |
Associated conditions | Multiple sclerosis [87,88,90], spinal cord injury [19,100,101], cerebral infarction [102,103], blood–brain barrier disruption [93] | Allergic asthma [92], respiratory inflammation [92], promotes respiratory tolerance through binding to PD-L2 [104] | Anemia of chronic disease (ACD) [14,98], hereditary hemochromatosis type 2 [14], inflammatory anemia [83,98,99] |
Possible involvement in ACD | RGMa is involved in neuroinflammatory diseases and promotes hepcidin expression through the BMP/SMAD pathway, suggesting a potential contribution to ACD associated with chronic neuroinflammation [78,87,88,90] | RGMb negatively regulates IL-6 expression and influences the BMP/SMAD pathway, potentially indirectly contributing to ACD pathogenesis through modulation of inflammatory responses [94,97] | HJV is essential for hepcidin induction during chronic inflammation and directly involved in the pathophysiology of ACD [14,98] |
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Fujii, T.; Kobayashi, K.; Kaneko, M.; Osana, S.; Tsai, C.-T.; Ito, S.; Hata, K. RGM Family Involved in the Regulation of Hepcidin Expression in Anemia of Chronic Disease. Immuno 2024, 4, 266-285. https://doi.org/10.3390/immuno4030017
Fujii T, Kobayashi K, Kaneko M, Osana S, Tsai C-T, Ito S, Hata K. RGM Family Involved in the Regulation of Hepcidin Expression in Anemia of Chronic Disease. Immuno. 2024; 4(3):266-285. https://doi.org/10.3390/immuno4030017
Chicago/Turabian StyleFujii, Takako, Kumi Kobayashi, Masaki Kaneko, Shion Osana, Cheng-Ta Tsai, Susumu Ito, and Katsuhiko Hata. 2024. "RGM Family Involved in the Regulation of Hepcidin Expression in Anemia of Chronic Disease" Immuno 4, no. 3: 266-285. https://doi.org/10.3390/immuno4030017