Glucocorticoids promote iron overload in immune cells and metabolic tissues

• Applicant: Professorin Maja Vujic Spasic, Ph.D.
• Subject Area: Endocrinology, Diabetology, Metabolism ; Gastroenterology ; Cell Biology
• Term: from 2019 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 426045492

Iron is a vital micronutrient. Its cellular and systemic levels are controlled by iron hormone hepcidin. Imbalances in iron levels and hepcidin expression are characteristics of acquired and genetic iron disorders. Here we identified stress hormones, glucocorticoids (GCs), as profound modulators of iron homeostasis. We show that acute and chronic GCs treatments in mice affect iron levels via modulating the expression of hepcidin and ferroportin suggesting that disturbances in iron homeostasis may present an overlooked side effect of GCs therapy. Vice versa, we discovered that systemic iron overload in mice impaired GCs signaling implying for cellular resistance to GCs in iron-overload condition. In this proposal we aim to elucidate i) molecular signaling by which GCs affect iron homeostasis, ii) assess whether impaired iron homeostasis is present in patients with endogenous pathologic hypercorticolism, and iii) whether GC-resistance is a general hallmark of iron overload disorders, which will have significant clinical implication since progressive iron overload, in particularly in the liver, is considered the risk factor for the development of liver cirrhosis and hepatocellular carcinoma.

• DFG Programme: Research Grants