MiR-383-5p promotes schistosomiasis-induced liver fibrosis by targeting peroxiredoxin-3
Abstract Background Schistosomiasis-induced liver fibrosis, a major complication of infection, arises primarily from the host immune response to schistosome eggs. The mechanisms underlying the development of liver fibrosis remain unclear, but microRNAs (miRNAs) are thought to play a crucial role in...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-06-01
|
| Series: | Parasites & Vectors |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13071-025-06824-w |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849725265357307904 |
|---|---|
| author | Yi-Xin Li Xin-Yue Zhang Ju-Lu Lu Ying-Ying Yang Cong-Jin Mei Pan-Pan Dong Chuan-Xin Yu Jian-Feng Zhang Chun-Rong Xiong Li-Jun Song Kun Yang |
| author_facet | Yi-Xin Li Xin-Yue Zhang Ju-Lu Lu Ying-Ying Yang Cong-Jin Mei Pan-Pan Dong Chuan-Xin Yu Jian-Feng Zhang Chun-Rong Xiong Li-Jun Song Kun Yang |
| author_sort | Yi-Xin Li |
| collection | DOAJ |
| description | Abstract Background Schistosomiasis-induced liver fibrosis, a major complication of infection, arises primarily from the host immune response to schistosome eggs. The mechanisms underlying the development of liver fibrosis remain unclear, but microRNAs (miRNAs) are thought to play a crucial role in this process. Our previous study revealed significantly reduced miR-383-5p expression in patients with advanced schistosomiasis, particularly in those with newly developed disease, suggesting a possible association between miR-383-5p and fibrotic progression. This study explores the role and mechanism of miR-383-5p in schistosomiasis-induced liver fibrosis. Methods The target gene of miR-383-5p was predicted through bioinformatics analysis. The expression levels of miR-383-5p and its target gene in the livers of Schistosoma japonicum (S. japonicum)-infected mice were investigated. Dual-luciferase reporter assays and miR-383-5p mimics and inhibitors were transfected of into LX-2 cells to determine the regulation of miR-383-5p on its target gene. AAV-8-overexpressing miR-383-5p vector injected into mice infected with S. japonicum, the target gene expression level, fibrosis-related factors, and pathological changes of liver were evaluated. The target gene knockout mice were infected with S. japonicum, and the degree of liver fibrosis was detected. Results Target gene prediction identified peroxiredoxin 3 (PRDX3), a mitochondrial peroxidase that scavenges reactive oxygen species (ROS), as a target of miR-383-5p. During the progression of schistosome infection in mice, the expression level of miR-383-5p in the liver gradually decreased, reaching its lowest level 6 weeks after infection, at the peak of inflammation in egg granulomas, then gradually increasing, while the expression kinetics of PRDX3 were opposite to those of miR-383-5p. Using dual-luciferase reporter assays and transfection of miR-383-5p mimics and inhibitors into LX-2 cells, we confirmed that miR-383-5p directly targeted the 3′ untranslated region (UTR) of PRDX3, leading to decreased mRNA levels of PRDX3. AAV8-mediated miR-383-5p overexpression and PRDX3 knockout in the mice infected with S. japonicum led to increased hepatic ROS and promoted the schistosomiasis-induced liver fibrosis. Conclusions Our findings suggest that downregulating miR-383-5p after schistosome infection may alleviate liver inflammation by de-repressing PRDX3, thereby increasing ROS scavenging and reducing oxidative stress. This study elucidates the role of the miR-383-5p/PRDX3 axis in schistosomiasis-induced liver fibrosis, suggesting that PRDX3 is a potential therapeutic target for this disease. Graphical abstract |
| format | Article |
| id | doaj-art-423f82ed54604bb3a30f9731b1f971f3 |
| institution | DOAJ |
| issn | 1756-3305 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Parasites & Vectors |
| spelling | doaj-art-423f82ed54604bb3a30f9731b1f971f32025-08-20T03:10:31ZengBMCParasites & Vectors1756-33052025-06-0118111410.1186/s13071-025-06824-wMiR-383-5p promotes schistosomiasis-induced liver fibrosis by targeting peroxiredoxin-3Yi-Xin Li0Xin-Yue Zhang1Ju-Lu Lu2Ying-Ying Yang3Cong-Jin Mei4Pan-Pan Dong5Chuan-Xin Yu6Jian-Feng Zhang7Chun-Rong Xiong8Li-Jun Song9Kun Yang10National Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Provincial Medical Key Laboratory, Jiangsu Institute of Parasitic DiseasesNational Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Provincial Medical Key Laboratory, Jiangsu Institute of Parasitic DiseasesNational Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Provincial Medical Key Laboratory, Jiangsu Institute of Parasitic DiseasesNational Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Provincial Medical Key Laboratory, Jiangsu Institute of Parasitic DiseasesNational Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Provincial Medical Key Laboratory, Jiangsu Institute of Parasitic DiseasesNational Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Provincial Medical Key Laboratory, Jiangsu Institute of Parasitic DiseasesNational Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Provincial Medical Key Laboratory, Jiangsu Institute of Parasitic DiseasesNational Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Provincial Medical Key Laboratory, Jiangsu Institute of Parasitic DiseasesNational Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Provincial Medical Key Laboratory, Jiangsu Institute of Parasitic DiseasesNational Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Provincial Medical Key Laboratory, Jiangsu Institute of Parasitic DiseasesNational Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Provincial Medical Key Laboratory, Jiangsu Institute of Parasitic DiseasesAbstract Background Schistosomiasis-induced liver fibrosis, a major complication of infection, arises primarily from the host immune response to schistosome eggs. The mechanisms underlying the development of liver fibrosis remain unclear, but microRNAs (miRNAs) are thought to play a crucial role in this process. Our previous study revealed significantly reduced miR-383-5p expression in patients with advanced schistosomiasis, particularly in those with newly developed disease, suggesting a possible association between miR-383-5p and fibrotic progression. This study explores the role and mechanism of miR-383-5p in schistosomiasis-induced liver fibrosis. Methods The target gene of miR-383-5p was predicted through bioinformatics analysis. The expression levels of miR-383-5p and its target gene in the livers of Schistosoma japonicum (S. japonicum)-infected mice were investigated. Dual-luciferase reporter assays and miR-383-5p mimics and inhibitors were transfected of into LX-2 cells to determine the regulation of miR-383-5p on its target gene. AAV-8-overexpressing miR-383-5p vector injected into mice infected with S. japonicum, the target gene expression level, fibrosis-related factors, and pathological changes of liver were evaluated. The target gene knockout mice were infected with S. japonicum, and the degree of liver fibrosis was detected. Results Target gene prediction identified peroxiredoxin 3 (PRDX3), a mitochondrial peroxidase that scavenges reactive oxygen species (ROS), as a target of miR-383-5p. During the progression of schistosome infection in mice, the expression level of miR-383-5p in the liver gradually decreased, reaching its lowest level 6 weeks after infection, at the peak of inflammation in egg granulomas, then gradually increasing, while the expression kinetics of PRDX3 were opposite to those of miR-383-5p. Using dual-luciferase reporter assays and transfection of miR-383-5p mimics and inhibitors into LX-2 cells, we confirmed that miR-383-5p directly targeted the 3′ untranslated region (UTR) of PRDX3, leading to decreased mRNA levels of PRDX3. AAV8-mediated miR-383-5p overexpression and PRDX3 knockout in the mice infected with S. japonicum led to increased hepatic ROS and promoted the schistosomiasis-induced liver fibrosis. Conclusions Our findings suggest that downregulating miR-383-5p after schistosome infection may alleviate liver inflammation by de-repressing PRDX3, thereby increasing ROS scavenging and reducing oxidative stress. This study elucidates the role of the miR-383-5p/PRDX3 axis in schistosomiasis-induced liver fibrosis, suggesting that PRDX3 is a potential therapeutic target for this disease. Graphical abstracthttps://doi.org/10.1186/s13071-025-06824-wmiR-383-5pPRDX3ROSLiver fibrosisSchistosomiasis |
| spellingShingle | Yi-Xin Li Xin-Yue Zhang Ju-Lu Lu Ying-Ying Yang Cong-Jin Mei Pan-Pan Dong Chuan-Xin Yu Jian-Feng Zhang Chun-Rong Xiong Li-Jun Song Kun Yang MiR-383-5p promotes schistosomiasis-induced liver fibrosis by targeting peroxiredoxin-3 Parasites & Vectors miR-383-5p PRDX3 ROS Liver fibrosis Schistosomiasis |
| title | MiR-383-5p promotes schistosomiasis-induced liver fibrosis by targeting peroxiredoxin-3 |
| title_full | MiR-383-5p promotes schistosomiasis-induced liver fibrosis by targeting peroxiredoxin-3 |
| title_fullStr | MiR-383-5p promotes schistosomiasis-induced liver fibrosis by targeting peroxiredoxin-3 |
| title_full_unstemmed | MiR-383-5p promotes schistosomiasis-induced liver fibrosis by targeting peroxiredoxin-3 |
| title_short | MiR-383-5p promotes schistosomiasis-induced liver fibrosis by targeting peroxiredoxin-3 |
| title_sort | mir 383 5p promotes schistosomiasis induced liver fibrosis by targeting peroxiredoxin 3 |
| topic | miR-383-5p PRDX3 ROS Liver fibrosis Schistosomiasis |
| url | https://doi.org/10.1186/s13071-025-06824-w |
| work_keys_str_mv | AT yixinli mir3835ppromotesschistosomiasisinducedliverfibrosisbytargetingperoxiredoxin3 AT xinyuezhang mir3835ppromotesschistosomiasisinducedliverfibrosisbytargetingperoxiredoxin3 AT jululu mir3835ppromotesschistosomiasisinducedliverfibrosisbytargetingperoxiredoxin3 AT yingyingyang mir3835ppromotesschistosomiasisinducedliverfibrosisbytargetingperoxiredoxin3 AT congjinmei mir3835ppromotesschistosomiasisinducedliverfibrosisbytargetingperoxiredoxin3 AT panpandong mir3835ppromotesschistosomiasisinducedliverfibrosisbytargetingperoxiredoxin3 AT chuanxinyu mir3835ppromotesschistosomiasisinducedliverfibrosisbytargetingperoxiredoxin3 AT jianfengzhang mir3835ppromotesschistosomiasisinducedliverfibrosisbytargetingperoxiredoxin3 AT chunrongxiong mir3835ppromotesschistosomiasisinducedliverfibrosisbytargetingperoxiredoxin3 AT lijunsong mir3835ppromotesschistosomiasisinducedliverfibrosisbytargetingperoxiredoxin3 AT kunyang mir3835ppromotesschistosomiasisinducedliverfibrosisbytargetingperoxiredoxin3 |