Discovering ferroptosis in biliary epithelium during liver fibrosis
6 affiliations
- 1Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome
- 2Interdisciplinary Department of Well-Being, Health and Environment Sustainability (BESSA), Sapienza University of Rome, Rieti
- 3Department of Physiology and Pharmacology ‘V. Erspamer’, Sapienza University of Rome
- 4Department of Experimental Morphology and Microscopy, Integrated Research Center (PRAAB), Campus Biomedico University of Rome
- 5Department of Life Sciences, Health and Health Professions, LINK Campus University, Rome
- 6Division of Health Sciences, Department of Movement, Human and Health Sciences, University of Rome Foro Italico, Italy
Abstract
Ferroptosis is an iron-dependent regulated cell death characterized by iron accumulation and lipid peroxidation. The liver represents the primary site of iron-overload injury due to its role in iron metabolism, but the potential role of ferroptosis in the biliary epithelium is yet unknown. The study investigated the recruitment of ferroptosis under control conditions and after bile duct ligation (BDL), highlighting the effects of ferroptosis inducers and inhibitors in a cell line of cholangiocytes. In addition, we identified iron deposits through Perls Prussian blue as well as the presence of proteins such as ferritin, transferrin receptor 1 (CD71), glutathione peroxidase-4 (GPX4) and acyl-CoA synthetase long-chain family member 4 (ACSL4). The results showed an increase in the expression of ferritin, CD71 and ACSL4 in the BDL model, whereas GPX4 was reduced in the cholestatic model in comparison to the control. In addition, sorafenib failed to trigger ferroptosis in cholangiocytes, whereas erastin was a potent inducer. Conversely, ferrostatin-1 (Fer-1) did not inhibit ferroptosis, while β-mercaptoethanol (βME) could protect cholangiocytes from ferroptosis-induced cell death. All these findings are important for understanding the involvement of ferroptosis in cholangiocyte pathophysiology and may support additional studies regarding the possible application of ferroptosis modulators in the treatment of liver fibrosis.
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BibTeX
@article{mancinelli2026discovering,
title = {{Discovering ferroptosis in biliary epithelium during liver fibrosis}},
author = {Romina Mancinelli and Arianna Casini and Stefano Leone and Ludovica Ceci and Rosa Vaccaro and Antonella Di Sotto and Giorgio Vivacqua and Rosemarie Heyn and Ludovica Garro and Marco Tagliafierro and Filippo Maria Bassi and Emanuele Bocci and Andrea Bassi and Luigi Pannarale and Antonio Franchitto and Paolo Onori and Eugenio Gaudio},
journal = {European Journal of Histochemistry : EJH},
year = {2026},
month = oct,
doi = {10.4081/ejh.2026.4615},
url = {https://doi.org/10.4081/ejh.2026.4615},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Discovering ferroptosis in biliary epithelium during liver fibrosis
AU - Romina Mancinelli
AU - Arianna Casini
AU - Stefano Leone
AU - Ludovica Ceci
AU - Rosa Vaccaro
AU - Antonella Di Sotto
AU - Giorgio Vivacqua
AU - Rosemarie Heyn
AU - Ludovica Garro
AU - Marco Tagliafierro
AU - Filippo Maria Bassi
AU - Emanuele Bocci
AU - Andrea Bassi
AU - Luigi Pannarale
AU - Antonio Franchitto
AU - Paolo Onori
AU - Eugenio Gaudio
PY - 2026
DA - 2026/10/28
JO - European Journal of Histochemistry : EJH
DO - 10.4081/ejh.2026.4615
UR - https://doi.org/10.4081/ejh.2026.4615
AB - Ferroptosis is an iron-dependent regulated cell death characterized by iron accumulation and lipid peroxidation. The liver represents the primary site of iron-overload injury due to its role in iron metabolism, but the potential role of ferroptosis in the biliary epithelium is yet unknown. The study investigated the recruitment of ferroptosis under control conditions and after bile duct ligation (BDL), highlighting the effects of ferroptosis inducers and inhibitors in a cell line of cholangiocytes. In addition, we identified iron deposits through Perls Prussian blue as well as the presence of proteins such as ferritin, transferrin receptor 1 (CD71), glutathione peroxidase-4 (GPX4) and acyl-CoA synthetase long-chain family member 4 (ACSL4). The results showed an increase in the expression of ferritin, CD71 and ACSL4 in the BDL model, whereas GPX4 was reduced in the cholestatic model in comparison to the control. In addition, sorafenib failed to trigger ferroptosis in cholangiocytes, whereas erastin was a potent inducer. Conversely, ferrostatin-1 (Fer-1) did not inhibit ferroptosis, while β-mercaptoethanol (βME) could protect cholangiocytes from ferroptosis-induced cell death. All these findings are important for understanding the involvement of ferroptosis in cholangiocyte pathophysiology and may support additional studies regarding the possible application of ferroptosis modulators in the treatment of liver fibrosis.
SN - 1121-760X
SN - 2038-8306
ER -