Mining host candidate regulators of schistosomiasis-induced liver fibrosis in response to artesunate therapy through transcriptomics approach.
Background Artesunate (ART) has been reported to have an antifibrotic effect in various organs. The underlying mechanism has not been systematically elucidated. We aimed to clarify the effect of ART on liver fibrosis induced by Schistosoma japonicum (S. japonicum) in an experimentally infected roden...
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Online Access: | https://doi.org/10.1371/journal.pntd.0011626 https://doaj.org/article/83193386de204c31b73f3f1b6ab6be89 |
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ftdoajarticles:oai:doaj.org/article:83193386de204c31b73f3f1b6ab6be89 2023-11-12T04:13:57+01:00 Mining host candidate regulators of schistosomiasis-induced liver fibrosis in response to artesunate therapy through transcriptomics approach. Yajie Yuan Xinyue Lv Yahan Wu Youhong Weng Fangwei Dai Haojie Ding Riping Chen Bin Zheng Wenxia Zhao Qunbo Tong Jianzu Ding Di Lou Yunru Lai Xiaofeng Chu Longyou Zhao Shaohong Lu Qingming Kong 2023-09-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0011626 https://doaj.org/article/83193386de204c31b73f3f1b6ab6be89 EN eng Public Library of Science (PLoS) https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0011626&type=printable https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0011626 https://doaj.org/article/83193386de204c31b73f3f1b6ab6be89 PLoS Neglected Tropical Diseases, Vol 17, Iss 9, p e0011626 (2023) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2023 ftdoajarticles https://doi.org/10.1371/journal.pntd.0011626 2023-10-22T00:42:50Z Background Artesunate (ART) has been reported to have an antifibrotic effect in various organs. The underlying mechanism has not been systematically elucidated. We aimed to clarify the effect of ART on liver fibrosis induced by Schistosoma japonicum (S. japonicum) in an experimentally infected rodent model and the potential underlying mechanisms. Methods The effect of ART on hepatic stellate cells (HSCs) was assessed using CCK-8 and Annexin V-FITC/PI staining assays. The experimental model of liver fibrosis was established in the Mongolian gerbil model infected with S. japonicum cercariae and then treated with 20 mg/kg or 40 mg/kg ART. The hydroxyproline (Hyp) content, malondialdehyde (MDA) content, superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities in liver tissue were measured and histopathological changes of liver tissues were observed. Whole-transcriptome RNA sequencing (RNA-seq) of the liver tissues was performed. Differentially expressed genes (DEGs) were identified using bioinformatic analysis and verified by quantitative PCR (qPCR) and western blot assay. Results ART significantly inhibited the proliferation and induce the apoptosis of HSCs in a dose-dependent manner. In vivo, Hyp content decreased significantly in the ART-H group compared to the model (MOD) group and GPX activity was significantly higher in the ART-H group than in the MOD group. Besides, ART treatment significantly reduced collagen production (p <0.05). A total of 158 DEGs and 44 differentially expressed miRNAs related to ART-induced anti-schistosomiasis liver fibrosis were identified. The qPCR and western blot results of selected DEGs were consistent with the sequencing results. These DEGs were implicated in key pathways such as immune and inflammatory response, integrin-mediated signaling and toll-like receptor signaling pathways. Conclusion ART is effective against liver fibrosis using Mongolian gerbil model induced by S. japonicum infection. We identified host candidate regulators of schistosomiasis-induced ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 17 9 e0011626 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
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English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Yajie Yuan Xinyue Lv Yahan Wu Youhong Weng Fangwei Dai Haojie Ding Riping Chen Bin Zheng Wenxia Zhao Qunbo Tong Jianzu Ding Di Lou Yunru Lai Xiaofeng Chu Longyou Zhao Shaohong Lu Qingming Kong Mining host candidate regulators of schistosomiasis-induced liver fibrosis in response to artesunate therapy through transcriptomics approach. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Background Artesunate (ART) has been reported to have an antifibrotic effect in various organs. The underlying mechanism has not been systematically elucidated. We aimed to clarify the effect of ART on liver fibrosis induced by Schistosoma japonicum (S. japonicum) in an experimentally infected rodent model and the potential underlying mechanisms. Methods The effect of ART on hepatic stellate cells (HSCs) was assessed using CCK-8 and Annexin V-FITC/PI staining assays. The experimental model of liver fibrosis was established in the Mongolian gerbil model infected with S. japonicum cercariae and then treated with 20 mg/kg or 40 mg/kg ART. The hydroxyproline (Hyp) content, malondialdehyde (MDA) content, superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities in liver tissue were measured and histopathological changes of liver tissues were observed. Whole-transcriptome RNA sequencing (RNA-seq) of the liver tissues was performed. Differentially expressed genes (DEGs) were identified using bioinformatic analysis and verified by quantitative PCR (qPCR) and western blot assay. Results ART significantly inhibited the proliferation and induce the apoptosis of HSCs in a dose-dependent manner. In vivo, Hyp content decreased significantly in the ART-H group compared to the model (MOD) group and GPX activity was significantly higher in the ART-H group than in the MOD group. Besides, ART treatment significantly reduced collagen production (p <0.05). A total of 158 DEGs and 44 differentially expressed miRNAs related to ART-induced anti-schistosomiasis liver fibrosis were identified. The qPCR and western blot results of selected DEGs were consistent with the sequencing results. These DEGs were implicated in key pathways such as immune and inflammatory response, integrin-mediated signaling and toll-like receptor signaling pathways. Conclusion ART is effective against liver fibrosis using Mongolian gerbil model induced by S. japonicum infection. We identified host candidate regulators of schistosomiasis-induced ... |
format |
Article in Journal/Newspaper |
author |
Yajie Yuan Xinyue Lv Yahan Wu Youhong Weng Fangwei Dai Haojie Ding Riping Chen Bin Zheng Wenxia Zhao Qunbo Tong Jianzu Ding Di Lou Yunru Lai Xiaofeng Chu Longyou Zhao Shaohong Lu Qingming Kong |
author_facet |
Yajie Yuan Xinyue Lv Yahan Wu Youhong Weng Fangwei Dai Haojie Ding Riping Chen Bin Zheng Wenxia Zhao Qunbo Tong Jianzu Ding Di Lou Yunru Lai Xiaofeng Chu Longyou Zhao Shaohong Lu Qingming Kong |
author_sort |
Yajie Yuan |
title |
Mining host candidate regulators of schistosomiasis-induced liver fibrosis in response to artesunate therapy through transcriptomics approach. |
title_short |
Mining host candidate regulators of schistosomiasis-induced liver fibrosis in response to artesunate therapy through transcriptomics approach. |
title_full |
Mining host candidate regulators of schistosomiasis-induced liver fibrosis in response to artesunate therapy through transcriptomics approach. |
title_fullStr |
Mining host candidate regulators of schistosomiasis-induced liver fibrosis in response to artesunate therapy through transcriptomics approach. |
title_full_unstemmed |
Mining host candidate regulators of schistosomiasis-induced liver fibrosis in response to artesunate therapy through transcriptomics approach. |
title_sort |
mining host candidate regulators of schistosomiasis-induced liver fibrosis in response to artesunate therapy through transcriptomics approach. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2023 |
url |
https://doi.org/10.1371/journal.pntd.0011626 https://doaj.org/article/83193386de204c31b73f3f1b6ab6be89 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 17, Iss 9, p e0011626 (2023) |
op_relation |
https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0011626&type=printable https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0011626 https://doaj.org/article/83193386de204c31b73f3f1b6ab6be89 |
op_doi |
https://doi.org/10.1371/journal.pntd.0011626 |
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PLOS Neglected Tropical Diseases |
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17 |
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9 |
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e0011626 |
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