Notum attenuates HBV-related liver fibrosis through inhibiting Wnt 5a mediated non-canonical pathways
Abstract Background Non-canonical Wnt pathways play important roles in liver fibrosis. Notum is a newly discovered inhibitor to Wnt proteins. This study was to investigate anti-fibrotic effects of Notum. Methods 53 patients with hepatitis B virus (HBV) infection as well as a cell co-culture system o...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-03-01
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| Series: | Biological Research |
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| Online Access: | http://link.springer.com/article/10.1186/s40659-019-0217-8 |
| _version_ | 1818851845743837184 |
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| author | Wenting Li Xiaolan Yu Chuanlong Zhu Zheng Wang Zonghao Zhao Yi Li Yonghong Zhang |
| author_facet | Wenting Li Xiaolan Yu Chuanlong Zhu Zheng Wang Zonghao Zhao Yi Li Yonghong Zhang |
| author_sort | Wenting Li |
| collection | DOAJ |
| description | Abstract Background Non-canonical Wnt pathways play important roles in liver fibrosis. Notum is a newly discovered inhibitor to Wnt proteins. This study was to investigate anti-fibrotic effects of Notum. Methods 53 patients with hepatitis B virus (HBV) infection as well as a cell co-culture system of LX-2 and Hep AD38 cells were engaged in this study. Clinical, biological and virological data of each patient were analyzed. Cell viability was detected at different time points. mRNA and protein levels of NFATc1 (Nuclear factor of activated T-cells), Jnk, α-SMA, Col1A1 and TIMP-1 were detected both in LX-2 and liver tissue. Protein levels of NFATc1 and Jnk in liver tissue and their correlations with fibrosis score were analyzed. Results Hepatitis B virus replication up-regulated Wnt5a induced NFATc1 and Jnk activity in Hep AD38. Notum suppressed NFATc1, Jnk and fibrosis genes expression, reduced cell viability in co-cultured LX-2 cells induced by HBV. Interestingly, Patients with HBV DNA > 5log copies/ml had higher mRNA levels of NFATc1 and fibrosis genes than patients with HBV DNA < 5log copies/ml. Most importantly, protein expressions of NFATc1 and pJnk have positive correlations with liver fibrosis scores in HBV-infected patients. Conclusions Our data showed that Notum inhibited HBV-induced liver fibrosis through down-regulating Wnt 5a mediated non-canonical pathways. This study shed light on anti-fibrotic treatment. |
| first_indexed | 2024-12-19T07:11:30Z |
| format | Article |
| id | doaj.art-ac9fe6e1e3f542db92420e79774e630c |
| institution | Directory Open Access Journal |
| issn | 0717-6287 |
| language | English |
| last_indexed | 2024-12-19T07:11:30Z |
| publishDate | 2019-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Biological Research |
| spelling | doaj.art-ac9fe6e1e3f542db92420e79774e630c2022-12-21T20:31:12ZengBMCBiological Research0717-62872019-03-0152111110.1186/s40659-019-0217-8Notum attenuates HBV-related liver fibrosis through inhibiting Wnt 5a mediated non-canonical pathwaysWenting Li0Xiaolan Yu1Chuanlong Zhu2Zheng Wang3Zonghao Zhao4Yi Li5Yonghong Zhang63rd Liver Unit, Department of Infectious Disease, Anhui Provincial HospitalDepartment of Ear-Nose-Throat, Anhui Provincial Hospital, Anhui Medical UniversityDepartment of Infectious Disease, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Respiratory and Critical Medicine, People’s Hospital of Zhengzhou University3rd Liver Unit, Department of Infectious Disease, Anhui Provincial Hospital3rd Liver Unit, Department of Infectious Disease, Anhui Provincial HospitalDepartment of General Surgery, The First Affiliated Hospital of Anhui Medical UniversityAbstract Background Non-canonical Wnt pathways play important roles in liver fibrosis. Notum is a newly discovered inhibitor to Wnt proteins. This study was to investigate anti-fibrotic effects of Notum. Methods 53 patients with hepatitis B virus (HBV) infection as well as a cell co-culture system of LX-2 and Hep AD38 cells were engaged in this study. Clinical, biological and virological data of each patient were analyzed. Cell viability was detected at different time points. mRNA and protein levels of NFATc1 (Nuclear factor of activated T-cells), Jnk, α-SMA, Col1A1 and TIMP-1 were detected both in LX-2 and liver tissue. Protein levels of NFATc1 and Jnk in liver tissue and their correlations with fibrosis score were analyzed. Results Hepatitis B virus replication up-regulated Wnt5a induced NFATc1 and Jnk activity in Hep AD38. Notum suppressed NFATc1, Jnk and fibrosis genes expression, reduced cell viability in co-cultured LX-2 cells induced by HBV. Interestingly, Patients with HBV DNA > 5log copies/ml had higher mRNA levels of NFATc1 and fibrosis genes than patients with HBV DNA < 5log copies/ml. Most importantly, protein expressions of NFATc1 and pJnk have positive correlations with liver fibrosis scores in HBV-infected patients. Conclusions Our data showed that Notum inhibited HBV-induced liver fibrosis through down-regulating Wnt 5a mediated non-canonical pathways. This study shed light on anti-fibrotic treatment.http://link.springer.com/article/10.1186/s40659-019-0217-8NotumWnt signaling pathwayHBVLiver fibrosis |
| spellingShingle | Wenting Li Xiaolan Yu Chuanlong Zhu Zheng Wang Zonghao Zhao Yi Li Yonghong Zhang Notum attenuates HBV-related liver fibrosis through inhibiting Wnt 5a mediated non-canonical pathways Biological Research Notum Wnt signaling pathway HBV Liver fibrosis |
| title | Notum attenuates HBV-related liver fibrosis through inhibiting Wnt 5a mediated non-canonical pathways |
| title_full | Notum attenuates HBV-related liver fibrosis through inhibiting Wnt 5a mediated non-canonical pathways |
| title_fullStr | Notum attenuates HBV-related liver fibrosis through inhibiting Wnt 5a mediated non-canonical pathways |
| title_full_unstemmed | Notum attenuates HBV-related liver fibrosis through inhibiting Wnt 5a mediated non-canonical pathways |
| title_short | Notum attenuates HBV-related liver fibrosis through inhibiting Wnt 5a mediated non-canonical pathways |
| title_sort | notum attenuates hbv related liver fibrosis through inhibiting wnt 5a mediated non canonical pathways |
| topic | Notum Wnt signaling pathway HBV Liver fibrosis |
| url | http://link.springer.com/article/10.1186/s40659-019-0217-8 |
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