STAT3 Promotes Schistosome-Induced Liver Injury by Inflammation, Oxidative Stress, Proliferation, and Apoptosis Signal Pathway
| Autor: | Jie Zhao, Lin-Shuang Zhang, Shi-Meng Liu, Xin Liu, Deng-Ren Ji, Feng-Min Lu, Yong-Hong Zhu, Ya-Rong Zhang, Yong-Fen Qi, Yao Chen, Yan-Rong Yu, Mo-Zhi Jia |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Liver Cirrhosis STAT3 Transcription Factor Immunology Inflammation Apoptosis medicine.disease_cause Microbiology Schistosoma japonicum Transcriptome 03 medical and health sciences 0302 clinical medicine Fibrosis medicine Animals STAT3 Cell Proliferation Liver injury biology medicine.disease Oxidative Stress 030104 developmental biology Infectious Diseases 030220 oncology & carcinogenesis Schistosomiasis japonica biology.protein STAT protein Cancer research Parasitology medicine.symptom Fungal and Parasitic Infections Oxidative stress |
| Zdroj: | Infect Immun |
| ISSN: | 1098-5522 |
| Popis: | 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 Stat3flox/flox Alb-Cre mice were infected with cercariae of Schistosoma japonicum. 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 Schistosoma-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 S. japonicum-induced liver fibrosis initiation. Meanwhile, we observed activation of the STAT3 pathway in hepatic injury during S. japonicum 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 S. japonicum-induced liver injury and may be a new potential guideline for the treatment of schistosomiasis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|