Hepcidin and the BMP-SMAD pathway: An unexpected liaison

Vitamins and Hormones
Laura SilvestriA Pagani

Abstract

Hepcidin, the main regulator of iron metabolism, is synthesized and released by hepatocytes in response to increased body iron concentration and inflammation. Deregulation of hepcidin expression is a common feature of genetic and acquired iron disorders: in Hereditary Hemochromatosis (HH) and iron-loading anemias low hepcidin causes iron overload, while in Iron Refractory Iron Deficiency Anemia (IRIDA) and anemia of inflammation (AI), high hepcidin levels induce iron-restricted erythropoiesis. Hepcidin expression in the liver is mainly controlled by the BMP-SMAD pathway, activated in a paracrine manner by BMP2 and BMP6 produced by liver sinusoidal endothelial cells. The BMP type I receptors ALK2 and ALK3 are responsible for iron-dependent hepcidin upregulation and basal hepcidin expression, respectively. Characterization of animal models with genetic inactivation of the key components of the pathway has suggested the existence of two BMP/SMAD pathway branches: the first ALK3 and HH proteins dependent, responsive to BMP2 for basal hepcidin activation, and the second ALK2 dependent, activated by BMP6 in response to increased tissue iron. The erythroid inhibitor of hepcidin Erythroferrone also impacts on the liver BMP-SMAD pathway...Continue Reading

Citations

Sep 1, 2019·Medicinal Research Reviews·Zhong-Ming Qian, Ya Ke
Mar 11, 2020·Hematology·Zhen ChengXiang-Tao Pan
Nov 30, 2019·Pharmaceuticals·Zachary J HawulaGautam Rishi
Aug 28, 2020·Investigative Ophthalmology & Visual Science·Anil TiwariShivalingappa K Swamynathan
May 1, 2019·Nature Metabolism·Sandro Altamura, Bruno Galy
Feb 15, 2020·Haematologica·Alessia PaganiLaura Silvestri
Oct 24, 2020·Expert Review of Anti-infective Therapy·Lara Valente de SouzaGünter Weiss
Oct 16, 2020·Haematologica·Alessia PaganiLaura Silvestri
May 25, 2021·Clinical Case Reports·Wenke MorisCees Th B M van Deursen
May 25, 2021·Frontiers in Molecular Biosciences·Ming-Li ZouFeng-Lai Yuan
Jun 8, 2021·Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS)·Yuhua LeiYan-Zhong Chang
Aug 15, 2021·Seminars in Hematology·Laura Silvestri, Antonella Nai
May 14, 2021·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Silvia ColucciMartina U Muckenthaler
Sep 10, 2021·Antioxidants & Redox Signaling·Hassan Mustafa ArifRui Wang
Oct 29, 2021·Growth Factors·Andrea Marlene García MuroJosefina Yoaly Sánchez López

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