PR/SET domain 1 targeting glutathione peroxidase 4 regulates chronic hepatitis B liver fibrosis through ferroptosis

作者：Wenjun Wu, Wujian Ke, Weiping Shi, Ting Lin, Shenglong Lin, Minghua Lin, Huaxi Ma, Haibing Gao · 发表于：CytoJournal · 年份：2024 · DOI：10.25259/cytojournal_123_2024 · 被引用次数：7 · 研究领域：Ferroptosis and cancer prognosis、Liver physiology and pathology、Liver Diseases and Immunity

Objective: Addressing the inhibition and reversal of chronic hepatitis B fibrosis is an urgent global challenge, which highlights the critical need to understand its underlying mechanisms. Inhibiting the activation of hepatic stellate cells (HSCs) is an important strategy for fibrosis reversal. In particular, the induction of ferroptosis in HSCs presents a promising avenue for curtailing liver fibrosis. Therefore, this study explores the influence of PR/SET domain 1 (PRDM1), which is a transcriptional regulator, on the progression of liver fibrosis by regulating HSC ferroptosis through glutathione peroxidase 4 (GPX4). Material and Methods: We used protein-protein interaction databases to analyze the interacting proteins of GPX4. The messenger ribonucleic acid levels of PRDM1 and GPX4 in liver tissues with varying degrees of fibrosis were examined using quantitative polymerase chain reaction. Cell lines with interference and overexpression of PRDM1/GPX4 were established. Reactive oxygen species (ROS) activity, malondialdehyde (MDA) concentration, cell proliferation capacity, as well as the expression levels of GPX4, a-smooth muscle actin, vimentin, and desmin, were assessed to investigate the relationship between PRDM1 and hepatic fibrosis, as well as its impact on ferroptosis in HSCs. Results: A significant negative correlation was observed between the transcriptional regulator PRDM1 and GPX4. As the degree of fibrosis worsened, PRDM1 decreased significantly, whereas GPX4 inc...