Journal article
The BMP-SMAD pathway mediates the impaired hepatic iron metabolism associated with the ERFE-A260S variant
American journal of hematology, v 94(11), pp 1227-1235
Nov 2019
PMID: 31400017
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The erythroferrone (ERFE) is the erythroid regulator of hepatic iron metabolism by suppressing the expression of hepcidin. Congenital dyserythropoietic anemia type II (CDAII) is an inherited hyporegenerative anemia due to biallelic mutations in the SEC23B gene. Patients with CDAII exhibit marked clinical variability, even among individuals sharing the same pathogenic variants. The ERFE expression in CDAII is increased and related to abnormal erythropoiesis. We identified a recurrent low-frequency variant, A260S, in the ERFE gene in 12.5% of CDAII patients with a severe phenotype. We demonstrated that the ERFE-A260S variant leads to increased levels of ERFE, with subsequently marked impairment of iron regulation pathways at the hepatic level. Functional characterization of ERFE-A260S in the hepatic cell system demonstrated its modifier role in iron overload by impairing the BMP/SMAD pathway. We herein described for the first time an ERFE polymorphism as a genetic modifier variant. This was with a mild effect on disease expression, under a multifactorial-like model, in a condition of iron-loading anemia due to ineffective erythropoiesis.
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Details
- Title
- The BMP-SMAD pathway mediates the impaired hepatic iron metabolism associated with the ERFE-A260S variant
- Creators
- Immacolata Andolfo - University of Naples Federico IIBarbara Eleni Rosato - University of Naples Federico IIRoberta Marra - University of Naples Federico IIGianluca De Rosa - University of Naples Federico IIFrancesco Manna - Ceinge Biotecnologie AvanzateAntonella Gambale - Ceinge Biotecnologie AvanzateAchille Iolascon - University of Naples Federico IIRoberta Russo - University of Naples Federico II
- Publication Details
- American journal of hematology, v 94(11), pp 1227-1235
- Publisher
- Wiley
- Grant note
- DGRC2362/07 / Regione Campania SIR/RBSI144KXC / Ministry of Education, Universities and Research CoDysAn / Spanish foundation "Ramón Areces"
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000484163200001
- Scopus ID
- 2-s2.0-85071465119
- Other Identifier
- 991022004874304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Hematology