Department of Infection, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Environ Toxicol. 2023 Dec;38(12):2803-2818. doi: 10.1002/tox.23906. Epub 2023 Sep 23.
This study investigated the effects of estrogen and estrogen receptor alpha (ERα) on the pathogenesis of primary biliary cholangitis (PBC) in human intrahepatic bile duct epithelial cells (HiBECs). The researchers measured serum levels of ERα, oxidative stress indicators, and cytokines in PBC patients and healthy controls. They examined the expression of ERα, pyruvate dehydrogenase complex E2-component (PDC-E2), and apoptosis-related proteins in the small bile ducts. In vitro experiments with HiBECs showed that estrogen had a dual effect on cell viability, increasing it at low concentrations but reducing it at higher concentrations. ERα activation led to mitochondrial damage, apoptosis, and upregulation of ERα and PDC-E2 expression. These findings suggest that the high expression of ERα in the bile ducts contributes to mitochondrial damage, inflammation, and apoptosis in PBC. The study highlights ERα as a potential target for understanding and treating estrogen-mediated PBC pathogenesis.
本研究探讨了雌激素和雌激素受体 α（ERα）对原发性胆汁性胆管炎（PBC）在人肝内胆管上皮细胞（HiBECs）发病机制中的影响。研究人员测量了 PBC 患者和健康对照组的血清 ERα、氧化应激指标和细胞因子水平。他们检查了小胆管中 ERα、丙酮酸脱氢酶复合物 E2 成分（PDC-E2）和凋亡相关蛋白的表达。HiBECs 的体外实验表明，雌激素对细胞活力具有双重作用，在低浓度时增加，在高浓度时减少。ERα 激活导致线粒体损伤、凋亡和 ERα 和 PDC-E2 表达上调。这些发现表明，胆管中 ERα 的高表达导致 PBC 中的线粒体损伤、炎症和凋亡。该研究强调 ERα 是理解和治疗雌激素介导的 PBC 发病机制的潜在靶点。
