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Blood. 2017 Jan 26;129(4):415-419. doi: 10.1182/blood-2016-07-729822. Epub 2016 Nov 30.

Angiocrine Bmp2 signaling in murine liver controls normal iron homeostasis.

Author information

1
Department of Dermatology, Venereology and Allergology, Center of Excellence in Dermatology.
2
Center for Medical Research.
3
Institute of Clinical Radiology and Nuclear Medicine.
4
Institute for Clinical Chemistry, and.
5
Section of Molecular Hepatology, Second Medical Department, University Medical Center and Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
6
Experimental Histopathology Laboratory, The Francis Crick Institute, London, United Kingdom; and.
7
Division of Molecular Immunology, and.
8
Division of Cellular Immunology, German Cancer Research Center, Heidelberg, Germany.

Abstract

Microvascular endothelial cells (ECs) display a high degree of phenotypic and functional heterogeneity among different organs. Organ-specific ECs control their tissue microenvironment by angiocrine factors in health and disease. Liver sinusoidal endothelial cells (LSECs) are uniquely differentiated to fulfill important organ-specific functions in development, under homeostatic conditions, and in regeneration and liver pathology. Recently, Bmp2 has been identified by us as an organ-specific angiokine derived from LSECs. To study angiocrine Bmp2 signaling in the liver, we conditionally deleted Bmp2 in LSECs using EC subtype-specific Stab2-Cre mice. Genetic inactivation of hepatic angiocrine Bmp2 signaling in Stab2-Cre;Bmp2fl/fl (Bmp2LSECKO) mice caused massive iron overload in the liver and increased serum iron levels and iron deposition in several organs similar to classic hereditary hemochromatosis. Iron overload was mediated by decreased hepatic expression of hepcidin, a key regulator of iron homeostasis. Thus, angiocrine Bmp2 signaling within the hepatic vascular niche represents a constitutive pathway indispensable for iron homeostasis in vivo that is nonredundant with Bmp6. Notably, we demonstrate that organ-specific angiocrine signaling is essential not only for the homeostasis of the respective organ but also for the homeostasis of the whole organism.

PMID:
27903529
PMCID:
PMC5291964
DOI:
10.1182/blood-2016-07-729822
[Indexed for MEDLINE]
Free PMC Article

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