The immunophilin FKBP12 inhibits hepcidin expression by binding the BMP type I receptor ALK2 in hepatocytes
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Key Points: FKBP12 suppresses hepcidin by interaction with the BMP receptor ALK2. Disruption of FKBP12–ALK2 interaction increases hepcidin and renders the receptor responsive to the inflammatory ligand Activin A.
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Another local inhibitor, the immunophillin FKBP12, binds the BMP receptor ALK2, suppressing the pathway activation.
“Another local inhibitor, the immunophillin FKBP12, binds the BMP receptor ALK2, suppressing the pathway activation.51”
From Iron metabolism and iron disorders revisited in the hepcidin era (2020) · cites this paper as [51]
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Cites
Identification of erythroferrone as an erythroid regulator of iron metabolism
Kautz, L., Jung, G., Valore, E. V., Rivella, S., Nemeth, E., & Ganz, T. (2014) · Nature Genetics · doi:10.1038/ng.2996 · Cited by 1,127 · see citing works
Hatsell, S. J., Idone, V., Wolken, D. M. A., Huang, L., Kim, H. J., Wang, L., Wen, X., Nannuru, K. C., Jimenez, J., Xie, L., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aac4358 · Cited by 446 · see citing works
Arezes, J., Jung, G., Gabayan, V., Valore, E., Ruchala, P., Gulig, P. A., Ganz, T., Nemeth, E., & Bulut, Y. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2014.12.001 · Cited by 227 · cited 1× · see citing works
“We speculate that the synergism weobservedbetweenActivinAandhigh concentrationofBMP6might be relevant when inflammation/infections occur in severe iron loading by further enhancing hepcidin expression in the attempts of achieving the protective condition of hypoferremia.(47) Our results suggest that hepcidin productio…”
ResultPharmacologic inhibition of hepcidin expression reverses anemia of chronic inflammation in rats
Theurl, I., Schroll, A., Sonnweber, T., Nairz, M., Theurl, M., Willenbacher, W., Eller, K., Wolf, D., Seifert, M., Sun, C. C., et al. (2011) · Blood · doi:10.1182/blood-2011-03-345066 · Cited by 189 · see citing works
Besson-Fournier, C., Latour, C., Kautz, L., Bertrand, J., Ganz, T., Roth, M.-P., & Coppin, H. (2012) · Blood · doi:10.1182/blood-2012-02-411470 · Cited by 179 · see citing works
Low hepcidin accounts for the proinflammatory status associated with iron deficiency
Pagani, A., Nai, A., Corna, G., Bosurgi, L., Rovere-Querini, P., Camaschella, C., & Silvestri, L. (2011) · Blood · doi:10.1182/blood-2011-02-337212 · Cited by 138 · see citing works
Self-citationCanali, S., Core, A. B., Zumbrennen-Bullough, K. B., Merkulova, M., Wang, C.-Y., Schneyer, A. L., Pietrangelo, A., & Babitt, J. L. (2016) · Endocrinology · doi:10.1210/en.2015-1747 · Cited by 113 · see citing works
Mayeur, C., Leyton, P. A., Kolodziej, S. A., Yu, B., & Bloch, K. D. (2014) · Blood · doi:10.1182/blood-2014-04-572644 · Cited by 74 · see citing works
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Iron metabolism and iron disorders revisited in the hepcidin era
Camaschella, C., Nai, A., & Silvestri, L. (2020) · Haematologica · doi:10.3324/haematol.2019.232124 · Cited by 734 · see citing works
“Another local inhibitor, the immunophillin FKBP12, binds the BMP receptor ALK2, suppressing the pathway activation.(51) Erythroferrone (ERFE) is released by erythroid precursors stimulated by erythropoietin to suppress hepcidin expression and favor iron acquisition for hemoglobin synthesis.”
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- Authors
- Colucci, S., Pagani, A., Pettinato, M., Artuso, I., Nai, A., Camaschella, C., & Silvestri, L.
- Affiliations
- Vita-Salute San Raffaele University (IT)
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2017-11-09
- Volume
- 130
- Issue
- 19
- Pages
- 2111-2120
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC5755682
- OpenAlex
- W2753861986
- Cited by
- 62
- References
- 8
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 3 · 2023: 12 · 2022: 5 · 2021: 6 · 2020: 14 · 2019: 7 · 2018: 4 · 2017: 1
- FWCI
- 5.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Blood (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Micronutrient Interactions and Effects
- Keywords
- FKBP12, hepcidin, ALK2, BMP type I receptor, BMP/Smad signaling, iron homeostasis, hepatocytes, rapamycin, tacrolimus, immunophilins, activin A, mTOR inhibition
- MeSH terms
- Animals, Gene Expression Regulation, Male, Mutation, Signal Transduction, Tacrolimus, Sirolimus, Tacrolimus Binding Protein 1A, Hepatocytes, Activin Receptors, Type I, Mice, Smad Proteins, Matrix Metalloproteinases, Secreted, Hepcidins
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