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

• Final Report Year: 2025

Final Report Abstract

Iron is a vital micronutrient. Its cellular and systemic levels are controlled by the 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 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 cellular/tissue resistance to GCs in iron-overload condition. Our investigations uncovered novel molecular mechanisms by which GCs affect iron homeostasis and vice versa, demonstrated hepcidin changes in patients with endogenous pathologic hypercortisolism, and established GC-resistance is a hallmark of iron overload disorders.

Publications

• Iron at the Interface of Hepatocellular Carcinoma. International Journal of Molecular Sciences, 22(8), 4097.
  Paganoni, Rossana; Lechel, André & Vujic, Spasic Maja
  
• Hfe Actions in Kupffer Cells Are Dispensable for Hepatic and Systemic Iron Metabolism. International Journal of Molecular Sciences, 24(10), 8948.
  Knoop, Paul; Yilmaz, Dilay; Paganoni, Rossana; Steele-Perkins, Peter; Gruber, Andreas; Akdogan, Banu; Zischka, Hans; Leopold, Kerstin & Vujić, Spasić Maja Vujić
  
• Seasonal and fasting induced changes in iron metabolism in Djungarian hamsters. PLOS ONE, 18(11), e0293971.
  Kawach, Rawan; Diedrich, Victoria; Gruber, Andreas; Leopold, Kerstin; Herwig, Annika & Vujić, Spasić Maja
  
• Iron metabolism in a mouse model of hepatocellular carcinoma. Scientific Reports, 15(1).
  Yilmaz, Dilay; Tharehalli, Umesh; Paganoni, Rossana; Knoop, Paul; Gruber, Andreas; Chen, Yuexin; Dong, Rui; Leithäuser, Frank; Seufferlein, Thomas; Leopold, Kerstin; Lechel, André & Vujić, Spasić Maja