Department of Cardiology, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, Hunnan, China.
Department of Intensive Care Units, The Affiliated Nanhua Hospital, Hengyang Medical school, University of South China, Hengyang, Hunnan, China.
J Cell Physiol. 2022 Jul;237(7):2808-2824. doi: 10.1002/jcp.30780. Epub 2022 May 23.
Fibrosis is a common feature of fibrotic diseases that poses a serious threat to global health due to high morbidity and mortality in developing countries. There exist some chemical compounds and biomolecules associated with the development of fibrosis, including cytokines, hormones, and enzymes. Among them, glutathione peroxidase 4 (GPX4), as a selenoprotein antioxidant enzyme, is widely found in the embryo, testis, brain, liver, heart, and photoreceptor cells. Moreover, it is shown that GPX4 elicits diverse biological functions by suppressing phospholipid hydroperoxide at the expense of decreased glutathione (GSH), including loss of neurons, autophagy, cell repair, inflammation, ferroptosis, apoptosis, and oxidative stress. Interestingly, these processes are intimately related to the occurrence of fibrotic disease. Recently, GPX4 has been reported to exhibit a decline in fibrotic disease and inhibit fibrosis, suggesting that alterations of GPX4 can change the course or dictate the outcome of fibrotic disease. In this review, we summarize the role and underlying mechanisms of GPX4 in fibrosis diseases such as lung fibrosis, liver fibrosis, kidney fibrosis, cardiac fibrosis, and myelofibrosis.
纤维化是纤维性疾病的共同特征，由于发展中国家的高发病率和死亡率，对全球健康构成严重威胁。存在一些与纤维化发展相关的化学化合物和生物分子，包括细胞因子、激素和酶。其中，谷胱甘肽过氧化物酶 4（GPX4）作为一种硒蛋白抗氧化酶，广泛存在于胚胎、睾丸、大脑、肝脏、心脏和光感受器细胞中。此外，研究表明，GPX4 通过牺牲谷胱甘肽（GSH）来抑制磷脂氢过氧化物，从而发挥多种生物学功能，包括神经元丧失、自噬、细胞修复、炎症、铁死亡、细胞凋亡和氧化应激。有趣的是，这些过程与纤维性疾病的发生密切相关。最近，有报道称 GPX4 在纤维性疾病中表达下降并抑制纤维化，这表明 GPX4 的改变可以改变纤维性疾病的进程或决定其结局。在这篇综述中，我们总结了 GPX4 在肺纤维化、肝纤维化、肾纤维化、心肌纤维化和骨髓纤维化等纤维化疾病中的作用及其潜在机制。
