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Heme Oxygenase-1 Suppresses Wnt Signaling Pathway in Nonalcoholic Steatohepatitis-Related Liver Fibrosis
Joint Authors
Du, Jinghua
Ren, Weiguang
Zhang, Qingshan
Fu, Na
Han, Fang
Cui, Po
Li, Wencong
Kong, Lingbo
Zhao, Suxian
Wang, Rongqi
Zhang, Yuguo
Yang, Luting
Kong, Li
Nan, Yuemin
Source
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-15, 15 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-05-02
Country of Publication
Egypt
No. of Pages
15
Main Subjects
Abstract EN
Background and Aim.
Heme oxygenase-1 (HO-1) has been verified to play an important role in nonalcoholic steatohepatitis (NASH), but the mechanism remains unclear.
In this study, we aimed to clarify whether induction of HO-1 reverses steatofibrosis via suppression of the Wnt signaling pathway and to explore the potential mechanism of HO-1 on NASH-related liver fibrosis.
Methods.
Mice were fed with a methionine-choline-deficient (MCD) diet for 8 weeks to induce steatohepatitis-related liver fibrosis and were treated with HO-1 inducer Hemin and inhibitor ZnPP.
Mouse sera were collected for the biochemical analysis, and livers were obtained for further histological observation and gene expression analysis.
HSC-T6 cells were cultured for the in vitro study and were administrated with Hemin and si-HO-1 to induce or inhibit the expression of HO-1.
qPCR and Western blot were used to assess the mRNA and protein levels of genes.
Results.
MCD-fed mice developed marked macrovesicular steatosis, focal necrosis, and inflammatory infiltration and pericellular fibrosis in liver sections.
Administration of Hemin could significantly ameliorate the severity of steatosis, inflammation, and fibrosis and also could decrease the serum ALT and AST.
We demonstrated that HO-1 induction was able to downregulate the key regulator of the canonical Wnt pathway Wnt1 and the noncanonical Wnt pathway Wnt5a.
The downstream factors of the Wnt pathway β-catenin and NFAT5 were inhibited by Hemin, but GSK-3β was upregulated compared to the MCD group, which were consistent with the in vitro study.
Hemin markedly inhibited the TGF-β1/Smad signaling pathway in both in vivo and in vitro studies.
Conclusion.
Our study demonstrated that HO-1 inhibited the activation of canonical and noncanonical Wnt signaling pathways in NASH-related liver fibrosis.
Thus, these results may suggest a new therapeutic strategy for NASH-related liver fibrosis.
American Psychological Association (APA)
Du, Jinghua& Ren, Weiguang& Zhang, Qingshan& Fu, Na& Han, Fang& Cui, Po…[et al.]. 2020. Heme Oxygenase-1 Suppresses Wnt Signaling Pathway in Nonalcoholic Steatohepatitis-Related Liver Fibrosis. BioMed Research International،Vol. 2020, no. 2020, pp.1-15.
https://search.emarefa.net/detail/BIM-1134299
Modern Language Association (MLA)
Du, Jinghua…[et al.]. Heme Oxygenase-1 Suppresses Wnt Signaling Pathway in Nonalcoholic Steatohepatitis-Related Liver Fibrosis. BioMed Research International No. 2020 (2020), pp.1-15.
https://search.emarefa.net/detail/BIM-1134299
American Medical Association (AMA)
Du, Jinghua& Ren, Weiguang& Zhang, Qingshan& Fu, Na& Han, Fang& Cui, Po…[et al.]. Heme Oxygenase-1 Suppresses Wnt Signaling Pathway in Nonalcoholic Steatohepatitis-Related Liver Fibrosis. BioMed Research International. 2020. Vol. 2020, no. 2020, pp.1-15.
https://search.emarefa.net/detail/BIM-1134299
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1134299