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 syst...

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Autores principales:	Li,Wenting, Yu,Xiaolan, Zhu,Chuanlong, Wang,Zheng, Zhao,Zonghao, Li,Yi, Zhang,Yonghong
Lenguaje:	English
Publicado:	Sociedad de Biología de Chile 2019
Materias:	Notum Wnt signaling pathway HBV Liver fibrosis
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602019000100208
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spelling	oai:scielo:S0716-976020190001002082019-10-10Notum attenuates HBV-related liver fibrosis through inhibiting Wnt 5a mediated non-canonical pathwaysLi,WentingYu,XiaolanZhu,ChuanlongWang,ZhengZhao,ZonghaoLi,YiZhang,Yonghong Notum Wnt signaling pathway HBV Liver fibrosis 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.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.52 20192019-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602019000100208en10.1186/s40659-019-0217-8
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	Notum Wnt signaling pathway HBV Liver fibrosis
spellingShingle	Notum Wnt signaling pathway HBV Liver fibrosis Li,Wenting Yu,Xiaolan Zhu,Chuanlong Wang,Zheng Zhao,Zonghao Li,Yi Zhang,Yonghong Notum attenuates HBV-related liver fibrosis through inhibiting Wnt 5a mediated non-canonical pathways
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.
author	Li,Wenting Yu,Xiaolan Zhu,Chuanlong Wang,Zheng Zhao,Zonghao Li,Yi Zhang,Yonghong
author_facet	Li,Wenting Yu,Xiaolan Zhu,Chuanlong Wang,Zheng Zhao,Zonghao Li,Yi Zhang,Yonghong
author_sort	Li,Wenting
title	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_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_sort	notum attenuates hbv-related liver fibrosis through inhibiting wnt 5a mediated non-canonical pathways
publisher	Sociedad de Biología de Chile
publishDate	2019
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602019000100208
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Notum attenuates HBV-related liver fibrosis through inhibiting Wnt 5a mediated non-canonical pathways

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