Breaking the cycle of fibrosis: Ferroptosis as a therapeutic target (Review)

Abstract

Fibrosis, characterized by abnormal deposition of extracellular matrix, is a chronic disease that progressively remodels tissues, leading to organ failure, earning it the moniker the 'silent killer' of organ function. Recently, ferroptosis, a novel form of regulated cell death, has garnered attention in research; its molecular mechanisms, including the lipid peroxidation cascade, dysregulation of glutathione metabolism and imbalance in iron ion homeostasis, have been closely linked to the progression of fibrosis. The present review systematically elaborates on the process of fibrosis, the main mechanisms of ferroptosis and the role of ferroptosis in fibrosis. The review also discusses intervention strategies targeting the key signaling nodes of ferroptosis during the inflammatory initiation and cell proliferation stages. In addition, it also elaborates on innovative therapeutic strategies based on regulating the ferroptosis pathway, including engineered exosome-mediated gene delivery systems and iron chelators encapsulated by multifunctional nanoparticles. Through a summary of current evidence, the present review provides a mechanistic rationale and new perspectives for the development of precision anti-fibrotic therapies targeting ferroptosis.