Department of Pathogen Biology, School of Basic Medical Sciences, Peking University, Beijing, China.
Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University Health Science Center, Beijing, China.
Infect Immun. 2021 Feb 16;89(3). doi: 10.1128/IAI.00309-20.
Schistosomiasis is a parasitic helminth disease that can cause organ lesions leading to health damage. During a schistosome infection, schistosome eggs can flow into the liver along the portal vein. Numerous inflammatory cells gather around the eggs, causing granulomas and fibrosis in the liver. In this process, many molecules are involved in the initiation and regulation of the fibrous scar formation. However, the precise molecular mechanisms responsible for the progression of granuloma formation and fibrosis initiation caused by schistosome infection have not been extensively studied. In this study, C57BL/6 wild-type mice and mice were infected with cercariae of Liver injury, effector molecule levels, and RNA transcriptome resequencing of liver tissue were detected at 4, 5, and 6 weeks postinfection. We investigated the role of STAT3 (signal transducer and activator of transcription 3) in -induced liver injury in mice. After 6 weeks postinfection, there was obvious liver fibrosis. A sustained pathological process (inflammation, oxidative stress, proliferation, and apoptosis) occurred in -induced liver fibrosis initiation. Meanwhile, we observed activation of the STAT3 pathway in hepatic injury during infection by RNA transcriptome resequencing. Liver deficiency of phospho-STAT3 alleviated infection-induced liver dysfunction, hepatic granuloma formation, and fibrosis initiation. It also promoted STAT3-dependent apoptosis and reduced liver inflammation, oxidative stress, and proliferation. Our results suggest that STAT3 signal pathway and its mediating inflammation, oxidative stress, proliferation, and apoptosis are involved in -induced liver injury and may be a new potential guideline for the treatment of schistosomiasis.
血吸虫病是一种寄生虫引起的蠕虫病，可导致器官损伤，从而对健康造成损害。在血吸虫感染过程中，血吸虫卵可随门静脉流入肝脏。大量炎性细胞聚集在虫卵周围，导致肝脏肉芽肿和纤维化。在这个过程中，许多分子参与了纤维疤痕形成的启动和调节。然而，对于由血吸虫感染引起的肉芽肿形成和纤维化启动的确切分子机制尚未得到广泛研究。在这项研究中，我们使用 C57BL/6 野生型小鼠和 小鼠感染尾蚴，在感染后 4、5 和 6 周检测肝脏损伤、效应分子水平和肝组织 RNA 转录组重测序。我们研究了 STAT3（信号转导和转录激活因子 3）在 诱导的小鼠肝脏损伤中的作用。感染 6 周后，肝脏出现明显的纤维化。在 诱导的肝纤维化启动过程中，发生了持续的病理过程（炎症、氧化应激、增殖和凋亡）。同时，我们通过 RNA 转录组重测序观察到在 感染期间 STAT3 途径在肝损伤中的激活。肝中磷酸化 STAT3 的缺乏减轻了感染引起的肝功能障碍、肝肉芽肿形成和纤维化启动。它还促进了 STAT3 依赖性细胞凋亡，减少了肝脏炎症、氧化应激和增殖。我们的结果表明，STAT3 信号通路及其介导的炎症、氧化应激、增殖和凋亡参与了 诱导的肝损伤，可能成为治疗血吸虫病的新潜在靶点。
