MicroRNA-122 protects against interferon-α-induced hepatic inflammatory response via the Janus kinase–signal transducer and activator of transcription pathway
Significant overlap in the epidemiology and coinfection of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) has been identified, which accelerates the development of severe liver cirrhosis and hepatocellular carcinoma worldwide. Interferon-α (IFN-α), a cytokine with antiviral properties,...
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The Japan Endocrine Society
2025-01-01
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| Series: | Endocrine Journal |
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| Online Access: | https://www.jstage.jst.go.jp/article/endocrj/72/1/72_EJ24-0317/_html/-char/en |
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| author | Fanwei Liu Bowen Liu Shanshan Xu Yinhua Ni Xiaoli Liu |
| author_facet | Fanwei Liu Bowen Liu Shanshan Xu Yinhua Ni Xiaoli Liu |
| author_sort | Fanwei Liu |
| collection | DOAJ |
| description | Significant overlap in the epidemiology and coinfection of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) has been identified, which accelerates the development of severe liver cirrhosis and hepatocellular carcinoma worldwide. Interferon-α (IFN-α), a cytokine with antiviral properties, exerts profound physiological effects on innate immunity by regulating interferon-stimulated genes (ISGs) within cells. However, the underlying mechanism of IFN-α in hepatic inflammation remains to be fully elucidated. Here, we utilized LO2 cells treated with the recombinant IFN-α protein and conducted microRNA (miR) sequencing. MiR-122-3p and miR-122-5p_R+1 were the most enriched miRNAs involved in the pathogenesis of IFN-α-induced inflammatory responses and were significantly downregulated by IFN-α treatment. Furthermore, we identified interferon induced protein with tetratricopeptide repeats 1 (IFIT1) as a potential target gene of miR-122. IFN-α markedly increased the expression of proinflammatory cytokines and fibrogenic genes but decreased the mRNA expression of ISGs. Additionally, IFN-α significantly activated the NF-κB p-p65, MAPK p-p38, and Jak/STAT pathways to trigger inflammation. Importantly, supplementation with a miR-122 mimic significantly alleviated IFN-α-induced inflammation and induced IFIT1 expression in LO2 cells. Conversely, the suppression of miR-122 markedly exacerbated the inflammatory response triggered by IFN-α. Furthermore, silencing IFIT1 via an siRNA elicited an inflammatory response, whereas IFIT1 overexpression ameliorated hepatic inflammation and fibrosis in a manner comparable to that induced by IFN-α treatment. Taken together, our findings suggest that miR-122 and its target, IFIT1, reciprocally regulate the inflammatory response associated with IFN through the Jak/STAT pathway. |
| format | Article |
| id | doaj-art-509cd82a01f444a4b0434b9e39870ebd |
| institution | Kabale University |
| issn | 1348-4540 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | The Japan Endocrine Society |
| record_format | Article |
| series | Endocrine Journal |
| spelling | doaj-art-509cd82a01f444a4b0434b9e39870ebd2025-01-22T05:36:47ZengThe Japan Endocrine SocietyEndocrine Journal1348-45402025-01-01721536710.1507/endocrj.EJ24-0317endocrjMicroRNA-122 protects against interferon-α-induced hepatic inflammatory response via the Janus kinase–signal transducer and activator of transcription pathwayFanwei Liu0Bowen Liu1Shanshan Xu2Yinhua Ni3Xiaoli Liu4State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, ChinaState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, ChinaDepartment of Anesthesia, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, ChinaCollege of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, ChinaState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, ChinaSignificant overlap in the epidemiology and coinfection of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) has been identified, which accelerates the development of severe liver cirrhosis and hepatocellular carcinoma worldwide. Interferon-α (IFN-α), a cytokine with antiviral properties, exerts profound physiological effects on innate immunity by regulating interferon-stimulated genes (ISGs) within cells. However, the underlying mechanism of IFN-α in hepatic inflammation remains to be fully elucidated. Here, we utilized LO2 cells treated with the recombinant IFN-α protein and conducted microRNA (miR) sequencing. MiR-122-3p and miR-122-5p_R+1 were the most enriched miRNAs involved in the pathogenesis of IFN-α-induced inflammatory responses and were significantly downregulated by IFN-α treatment. Furthermore, we identified interferon induced protein with tetratricopeptide repeats 1 (IFIT1) as a potential target gene of miR-122. IFN-α markedly increased the expression of proinflammatory cytokines and fibrogenic genes but decreased the mRNA expression of ISGs. Additionally, IFN-α significantly activated the NF-κB p-p65, MAPK p-p38, and Jak/STAT pathways to trigger inflammation. Importantly, supplementation with a miR-122 mimic significantly alleviated IFN-α-induced inflammation and induced IFIT1 expression in LO2 cells. Conversely, the suppression of miR-122 markedly exacerbated the inflammatory response triggered by IFN-α. Furthermore, silencing IFIT1 via an siRNA elicited an inflammatory response, whereas IFIT1 overexpression ameliorated hepatic inflammation and fibrosis in a manner comparable to that induced by IFN-α treatment. Taken together, our findings suggest that miR-122 and its target, IFIT1, reciprocally regulate the inflammatory response associated with IFN through the Jak/STAT pathway.https://www.jstage.jst.go.jp/article/endocrj/72/1/72_EJ24-0317/_html/-char/eninterferon-αmicrorna (mir)-122ifn-induced proteins with tetratricopeptide repeats 1 (ifit1)inflammatory responsejanus kinase (jak)–signal transducer and activator of transcription (stat) pathway |
| spellingShingle | Fanwei Liu Bowen Liu Shanshan Xu Yinhua Ni Xiaoli Liu MicroRNA-122 protects against interferon-α-induced hepatic inflammatory response via the Janus kinase–signal transducer and activator of transcription pathway Endocrine Journal interferon-α microrna (mir)-122 ifn-induced proteins with tetratricopeptide repeats 1 (ifit1) inflammatory response janus kinase (jak)–signal transducer and activator of transcription (stat) pathway |
| title | MicroRNA-122 protects against interferon-α-induced hepatic inflammatory response via the Janus kinase–signal transducer and activator of transcription pathway |
| title_full | MicroRNA-122 protects against interferon-α-induced hepatic inflammatory response via the Janus kinase–signal transducer and activator of transcription pathway |
| title_fullStr | MicroRNA-122 protects against interferon-α-induced hepatic inflammatory response via the Janus kinase–signal transducer and activator of transcription pathway |
| title_full_unstemmed | MicroRNA-122 protects against interferon-α-induced hepatic inflammatory response via the Janus kinase–signal transducer and activator of transcription pathway |
| title_short | MicroRNA-122 protects against interferon-α-induced hepatic inflammatory response via the Janus kinase–signal transducer and activator of transcription pathway |
| title_sort | microrna 122 protects against interferon α induced hepatic inflammatory response via the janus kinase signal transducer and activator of transcription pathway |
| topic | interferon-α microrna (mir)-122 ifn-induced proteins with tetratricopeptide repeats 1 (ifit1) inflammatory response janus kinase (jak)–signal transducer and activator of transcription (stat) pathway |
| url | https://www.jstage.jst.go.jp/article/endocrj/72/1/72_EJ24-0317/_html/-char/en |
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