Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.
Department of Surgery, Third Clinical Medical College, Capital Medical University, Beijing 100020, China.
Chin Med J (Engl). 2024 Apr 5;137(7):806-817. doi: 10.1097/CM9.0000000000002784. Epub 2023 Sep 5.
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.
纤维化是一种普遍存在的修复过程的生理反应表现，其特征是细胞外基质成分的过度积累。然而，在反复或严重损伤的情况下，纤维化可能会失调，导致病理性状态和器官衰竭。近年来，一种新形式的受调控的细胞死亡，称为铁死亡，被认为可能是纤维化的一个促成因素；其特征是铁介导的脂质过氧化。由于越来越多的证据表明铁死亡与纤维生成有关，而纤维生成被认为是由潜在的炎症和免疫反应驱动的，因此铁死亡受到了关注。尽管人们对铁死亡与纤维化之间的关系越来越感兴趣，但对于铁死亡在纤维化组织形成中的确切作用仍缺乏全面的了解。本综述旨在综合以前与该主题相关的研究。我们将铁死亡可能导致纤维化的不同直接和间接机制分为三类：（1）铁过载毒性；（2）铁死亡引起的坏死性炎症，重点关注铁死亡和巨噬细胞相互作用；（3）铁死亡相关的促纤维化因子和途径。此外，本综述还考虑了这些发现的潜在意义，并强调了铁死亡靶向治疗作为减轻纤维化进展的有前途的策略的利用。总之，针对铁死亡的新型抗纤维化治疗可能是纤维化的有效治疗方法。
