Institute of Biology and Medical Sciences, Soochow University, Building 703, 199 Ren-ai Road, Suzhou 215123, China.
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Int Immunopharmacol. 2023 Mar;116:109812. doi: 10.1016/j.intimp.2023.109812. Epub 2023 Feb 4.
Fibrosis refers to the process of excessive deposition of extracellular matrix (ECM) proteins, eventually leading to excessive scar formation. Fibrotic diseases can occur in many organs and result in high mortality. Currently, there is no effective treatment for fibrosis. As a new form of regulatory cell death (RCD), ferroptosis is mainly mediated by iron overload and lipid peroxidation. Emerging evidence shows that ferroptosis is involved in the pathogenesis of fibrotic diseases. Generally, ferroptosis of parenchymal cells exacerbates the progression of fibrosis, while ferroptosis of myofibroblasts may ameliorate it. Therefore, studying the mechanisms of ferroptosis in fibrosis and targeting ferroptosis in certain cells can provide valuable insights into the pathogenesis of fibrotic diseases. In the present review, we summarized the mechanisms and regulators of ferroptosis and then described the mechanism of fibrosis and the role of ferroptosis in fibrotic diseases, including liver fibrosis, renal fibrosis, pulmonary fibrosis, and myocardial fibrosis.
纤维化是指细胞外基质(ECM)蛋白过度沉积的过程,最终导致过度的瘢痕形成。纤维化疾病可发生在许多器官中,并导致高死亡率。目前,纤维化尚无有效的治疗方法。铁死亡作为一种新的调控性细胞死亡(RCD)形式,主要由铁过载和脂质过氧化介导。新出现的证据表明,铁死亡参与了纤维化疾病的发病机制。一般来说,实质细胞的铁死亡会加重纤维化的进展,而肌成纤维细胞的铁死亡可能会减轻纤维化的进展。因此,研究纤维化中铁死亡的机制以及针对某些细胞中的铁死亡,可以为纤维化疾病的发病机制提供有价值的见解。在本综述中,我们总结了铁死亡的机制和调节因子,然后描述了纤维化的机制以及铁死亡在纤维化疾病中的作用,包括肝纤维化、肾纤维化、肺纤维化和心肌纤维化。