Role of ferroptosis in fibrosis:From mechanism to potential therapyOACSTPCDMEDLINE

Fibrosis,which is a manifestation of the physiological response to injury characterized by excessive accumulation of extracellular matrix components,is a ubiquitous outcome of the repair process.However,in cases of repetitive or severe injury,fibrosis may become dysregulated,leading to a pathological state and organ failure.In recent years,a novel form of regulated cell death,referred to as ferroptosis,has been identified as a possible contributor to fibrosis;it is characterized by iron-mediated lipid peroxidation.It has garnered attention due to the growing body of evidence linking ferroptosis and fibrogenesis,which is believed to be driven by underlying inflammation and immune responses.Despite the increasing interest in the relationship between ferroptosis and fibrosis,a comprehensive understanding of the precise role that ferroptosis plays in the formation of fibrotic tissue remains limited.This review seeks to synthesize previous research related to the topic.We categorized the different direct and indirect mechanisms by which ferroptosis may contribute to fibrosis into three categories:(1)iron overload toxicity;(2)ferroptosis-evoked necroinflammation,with a focus on ferroptosis and macrophage interplay;and(3)ferroptosis-associated pro-fibrotic factors and pathways.Furthermore,the review considers the potential implications of these findings and highlights the utilization of ferroptosis-targeted therapies as a promising strategy for mitigating the progression of fibrosis.In conclusion,novel anti-fibrotic treatments targeting ferroptosis could be an effective treatment for fibrosis.