Dysregulated Glucuronidation of Bilirubin Exacerbates Liver Inflammation and Fibrosis in Schistosomiasis Japonica through the NF-κB Signaling Pathway
Qingkai Xue,
Yuyan Wang,
Yiyun Liu,
Haiyong Hua,
Xiangyu Zhou,
Yongliang Xu,
Ying Zhang,
Chunrong Xiong,
Xinjian Liu,
Kun Yang,
Yuzheng Huang
Affiliations
Qingkai Xue
National Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, 117 Meiyuan Yangxiang, Wuxi 214064, China
Yuyan Wang
School of Public Health, Nanjing Medical University, Nanjing 211166, China
Yiyun Liu
National Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, 117 Meiyuan Yangxiang, Wuxi 214064, China
Haiyong Hua
National Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, 117 Meiyuan Yangxiang, Wuxi 214064, China
Xiangyu Zhou
National Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, 117 Meiyuan Yangxiang, Wuxi 214064, China
Yongliang Xu
National Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, 117 Meiyuan Yangxiang, Wuxi 214064, China
Ying Zhang
National Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, 117 Meiyuan Yangxiang, Wuxi 214064, China
Chunrong Xiong
National Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, 117 Meiyuan Yangxiang, Wuxi 214064, China
Xinjian Liu
Department of Pathogen Biology, Key Laboratory of Antibody Techniques of National Health Commission, Nanjing Medical University, Nanjing 211166, China
Kun Yang
National Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, 117 Meiyuan Yangxiang, Wuxi 214064, China
Yuzheng Huang
School of Public Health, Nanjing Medical University, Nanjing 211166, China
Hepatic fibrosis is an important pathological manifestation of chronic schistosome infection. Patients with advanced schistosomiasis show varying degrees of abnormalities in liver fibrosis indicators and bilirubin metabolism. However, the relationship between hepatic fibrosis in schistosomiasis and dysregulated bilirubin metabolism remains unclear. In this study, we observed a positive correlation between total bilirubin levels and the levels of ALT, AST, LN, and CIV in patients with advanced schistosomiasis. Additionally, we established mouse models at different time points following S. japonicum infection. As the infection time increased, liver fibrosis escalated, while liver UGT1A1 consistently exhibited a low expression, indicating impaired glucuronidation of bilirubin metabolism in mice. In vitro experiments suggested that SEA may be a key inhibitor of hepatic UGT1A1 expression after schistosome infection. Furthermore, a high concentration of bilirubin activated the NF-κB signaling pathway in L-O2 cells in vitro. These findings suggested that the dysregulated glucuronidation of bilirubin caused by S. japonicum infection may play a significant role in schistosomiasis liver fibrosis through the NF-κB signaling pathway.
