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Notum attenuates HBV-related liver fibrosis through inhibiting Wnt 5a mediated non-canonical pathways
Li, Wenting; Yu, Xiaolan; Zhu, Chuanlong; Wang, Zheng; Zhao, Zonghao; Li, Yi; Zhang, Yonghong.
  • Li, Wenting; Anhui Provincial Hospital. Department of Infectious Disease. Hefei. CN
  • Yu, Xiaolan; Anhui Medical University. Anhui Provincial Hospital. Department of Ear-Nose-Throat. Hefei. CN
  • Zhu, Chuanlong; The First Affiliated Hospital of Nanjing Medical University. Department of Infectious Disease. Nanjing. CN
  • Wang, Zheng; People's Hospital of Zhengzhou University. Department of Respiratory and Critical Medicine. Zhengzhou. CN
  • Zhao, Zonghao; Anhui Provincial Hospital. Department of Infectious Disease. Hefei. CN
  • Li, Yi; Anhui Provincial Hospital. Department of Infectious Disease. Hefei. CN
  • Zhang, Yonghong; The First Affiliated Hospital of Anhui Medical University. Department of General Surgery. Hefei. CN
Biol. Res ; 52: 10, 2019. tab, graf
Article in English | LILACS | ID: biblio-1011412
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.
Subject(s)


Full text: Available Index: LILACS (Americas) Main subject: Esterases / Wnt-5a Protein / Hepatitis B / Liver Cirrhosis Limits: Adult / Female / Humans / Male Language: English Journal: Biol. Res Journal subject: Biology Year: 2019 Type: Article Affiliation country: China Institution/Affiliation country: Anhui Medical University/CN / Anhui Provincial Hospital/CN / People's Hospital of Zhengzhou University/CN / The First Affiliated Hospital of Anhui Medical University/CN / The First Affiliated Hospital of Nanjing Medical University/CN

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Full text: Available Index: LILACS (Americas) Main subject: Esterases / Wnt-5a Protein / Hepatitis B / Liver Cirrhosis Limits: Adult / Female / Humans / Male Language: English Journal: Biol. Res Journal subject: Biology Year: 2019 Type: Article Affiliation country: China Institution/Affiliation country: Anhui Medical University/CN / Anhui Provincial Hospital/CN / People's Hospital of Zhengzhou University/CN / The First Affiliated Hospital of Anhui Medical University/CN / The First Affiliated Hospital of Nanjing Medical University/CN