title: The murine growth differentiation factor 15 is not essential for systemic iron homeostasis in phlebotomized mice.
abstract: In conditions of increased erythropoiesis, expression of hepcidin, the master regulator of systemic iron homeostasis, is decreased to allow for the release of iron into the blood stream from duodenal enterocytes and macrophages. It has been suggested that hepcidin suppression is controlled by growth differentiation factor 15 (GDF15), a member of the transforming growth factor-β superfamily of cytokines that is secreted from developing erythroblasts. In this study, we analyzed iron-related parameters in mice deficient for GDF15 under steady-state conditions and in response to increased erythropoietic activity induced by blood loss. We demonstrate that GDF15 suppresses the hepatic mRNA expression of some BMP/TGFβ target genes but not of hepcidin, and show that GDF15 is not required to balance iron homeostasis in response to blood loss.
authors.affiliation: Department of Pediatric Oncology, Hematology and Immunology, University Hospital of Heidelberg, Germany.
authors.forename: Guillem
authors.initials: G
authors.lastname: Casanovas
authors.forename: Maja
authors.initials: M
authors.lastname: Vujić Spasic
authors.forename: Carla
authors.initials: C
authors.lastname: Casu
authors.forename: Stefano
authors.initials: S
authors.lastname: Rivella
authors.forename: Jens
authors.initials: J
authors.lastname: Strelau
authors.forename: Klaus
authors.initials: K
authors.lastname: Unsicker
authors.forename: Martina U
authors.initials: MU
authors.lastname: Muckenthaler
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D004909:Erythrocyte Indices; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000235:genetics / Q000378:metabolism*; D064451:Hepcidins / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis; D007501:Iron / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018962:Phlebotomy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000378:metabolism
chemical_list: D055436:Growth Differentiation Factor 15; D064451:Hepcidins; D012333:RNA, Messenger; D007501:Iron