Project Details
Projekt
Identification of iron-related signals controlling BMP expression in liver non-parenchymal cells
Applicant
Professorin Dr. Martina Muckenthaler
Subject Area
Endocrinology, Diabetology, Metabolism
Anatomy and Physiology
Anatomy and Physiology
Term
since 2020
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 436298031
Control of systemic iron homeostasis evolved to maintain a plasma iron concentration that secures adequate supplies to tissues and cells while preventing organ iron overload. The small hepatocyte-derived peptide hormone hepcidin synchronizes systemic iron fluxes to control the amount of iron available in the circulation for cellular iron uptake (e.g. in bone cells). Hepcidin targets the iron export protein ferroportin to trigger its degradation, thus preventing dietary iron absorption and macrophage iron release. A fundamental question in iron biology still remains unanswered: how are iron levels sensed by the liver? Hepcidin mRNA expression in hepatocytes is controlled by the BMP/SMAD signaling pathway, whereby BMPs are expressed in liver non-parenchymal cells in response to changes in systemic iron levels. We hypothesize that a cross-talk of several liver cell types (hepatocytes, LSECs, stellate cells and Kupffer cells) will play a role for the hepcidin response to iron. By analyzing genetic mouse models of systemic iron overload and deficiency we will determine gene response patterns in all liver cell types and identify and validate pathways involved in the responses of BMPs to iron in primary cell (co) cultures. Additionally, we will test whether signals and pathways identified in the liver will also be operational in the bone for regulation of BMP levels.
DFG Programme
Research Units
