Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
October 2013 Volume 8 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
October 2013 Volume 8 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Recombinant human histidine triad nucleotide-binding protein 1 attenuates liver fibrosis induced by carbon tetrachloride in rats

  • Authors:
    • Fei Wu
    • Shaofang Huang
    • Nanlan Zhu
    • Wei Liu
    • Yanan Zhang
    • Yongwen He
  • View Affiliations / Copyright

    Affiliations: Department of Infectious Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
  • Pages: 1023-1028
    |
    Published online on: August 7, 2013
       https://doi.org/10.3892/mmr.2013.1618
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

It is currently thought that the transforming growth factor-β (TGF-β)/Smad signaling pathway acts as a central pathway leading to liver fibrosis, and that the aberrant Wnt/β-catenin signaling pathway also plays a vital role in the development of liver fibrosis. There is evidence that the histidine triad nucleotide-binding protein 1 (Hint1) was capable of inhibiting these two pathways. However, little data regarding the effects of Hint1 on liver fibrosis exists. Thus, we sought to investigate whether the recombinant human Hint1 protein (rhHint1) was capable of attenuating liver fibrosis induced by carbon tetrachloride (CCl4) in rats and the possible underlying mechanism(s) of action. In the present study, purified rhHint1 was obtained using genetic engineering technology. Liver fibrosis was induced in male Sprague-Dawley (SD) rats by the subcutaneous injection of CCl4. The rats were randomly divided into the normal control, the liver fibrosis model and the rhHint1 (doses, 50 and 100 µg/kg)‑treated groups. Following four weeks of treatment, the rhHint1-treated rats exhibited significantly reduced liver fibrosis upon histopathological analysis and lower levels of hydroxyproline. Furthermore, rhHint1 inhibited the expression of α-smooth muscle actin (α-SMA) in the liver tissues. Additionally, rhHint1 lowered the gene expression levels of TGF-β1/Smad3 and β-catenin/cyclin D1, whereas it increased the gene expression levels of Smad7. In conclusion, the results of this study indicated that rhHint1 is capable of attenuating CCl4-induced liver fibrosis by simultaneously targeting multiple pathogenic pathways, which may be developed as a new treatment for liver fibrosis.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Albanis E and Friedman SL: Hepatic fibrosis: Pathogenesis and principles of therapy. Clin Liver Dis. 5:315–334. 2001. View Article : Google Scholar : PubMed/NCBI

2 

Gutierrez-Reyes G, Gutierrez-Ruiz MC and Kershenobich D: Liver fibrosis and chronic viral hepatitis. Arch Med Res. 38:644–651. 2007. View Article : Google Scholar : PubMed/NCBI

3 

Friedman SL: Liver fibrosis - from bench to bedside. J Hepatol. 38:S38–S53. 2003. View Article : Google Scholar

4 

Parsons CJ, Takashima M and Rippe RA: Molecular mechanisms of hepatic fibrogenesis. J Gastroenterol Hepatol. 22:S79–S84. 2007. View Article : Google Scholar

5 

Gressner AM and Weiskirchen R: Modern pathogenetic concepts of liver fibrosis suggest stellate cells and TGF-beta as major players and therapeutic targets. J Cell Mol Med. 10:76–99. 2006. View Article : Google Scholar : PubMed/NCBI

6 

Inagaki Y and Okazaki I: Emerging insights into transforming growth factor beta Smad signal in hepatic fibrogenesis. Gut. 56:284–292. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Bataller R and Brenner DA: Liver fibrosis. J Clin Invest. 115:209–218. 2005. View Article : Google Scholar

8 

Sohrabpour AA, Mohamadnejad M and Malekzadeh R: Review article: the reversibility of cirrhosis. Aliment Pharmacol Ther. 36:824–832. 2012.PubMed/NCBI

9 

Varga J and Pasche B: Antitransforming growth factor-beta therapy in fibrosis: recent progress and implications for systemic sclerosis. Curr Opin Rheumatol. 20:720–728. 2008. View Article : Google Scholar : PubMed/NCBI

10 

de Gouville AC, Boullay V, Krysa G, et al: Inhibition of TGF-beta signaling by an ALK5 inhibitor protects rats from dimethylnitrosamine-induced liver fibrosis. Br J Pharmacol. 145:166–177. 2005.PubMed/NCBI

11 

Clevers H: Wnt/beta-catenin signaling in development and disease. Cell. 127:469–480. 2006. View Article : Google Scholar : PubMed/NCBI

12 

Cheng JH, She HY, Han YP, et al: Wnt antagonism inhibits hepatic stellate cell activation and liver fibrosis. Am J Physiol Gastrointest Liver Physiol. 294:G39–G49. 2008. View Article : Google Scholar : PubMed/NCBI

13 

Li W, Zhu C, Chen X, Li Y, Gao R and Wu Q: Pokeweed antiviral protein down-regulates Wnt/beta-catenin signalling to attenuate liver fibrogenesis in vitro and in vivo. Dig Liver Dis. 43:559–566. 2011. View Article : Google Scholar : PubMed/NCBI

14 

Thompson MD and Monga SP: WNT/beta-catenin signaling in liver health and disease. Hepatology. 45:1298–1305. 2007. View Article : Google Scholar : PubMed/NCBI

15 

Li WT, He YW, Xiao ZH and Ma YB: Effect of beta-catenin on the activation of hepatic stellate cells induced by transforming growth factor-beta1. Zhonghua Gan Zang Bing Za Zhi. 17:188–192. 2009.(In Chinese).

16 

Baarsma HA, Spanjer AI, Haitsma G, et al: Activation of WNT/beta-catenin signaling in pulmonary fibroblasts by TGF-beta1 is increased in chronic obstructive pulmonary disease. PLoS ONE. 6:e254502011. View Article : Google Scholar : PubMed/NCBI

17 

Tian X, Zhang J, Tan TK, et al: Association of beta-catenin with P-Smad3 but not LEF-1 differentiates in vitro profibrotic and anti-inflammatory effects of TGF-beta1. J Cell Sci. 2012.PubMed/NCBI

18 

Li H, Zhang Y, Su T, Santella RM and Weinstein IB: Hint1 is a haplo-insufficient tumor suppressor in mice. Oncogene. 25:713–721. 2006. View Article : Google Scholar : PubMed/NCBI

19 

Weiske J and Huber O: The histidine triad protein Hint1 triggers apoptosis independent of its enzymatic activity. J Biol Chem. 281:27356–27366. 2006. View Article : Google Scholar : PubMed/NCBI

20 

Huber O and Weiske J: Beta-catenin takes a HIT. Cell Cycle. 7:1326–1331. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Weiske J and Huber O: The histidine triad protein Hint1 interacts with Pontin and Reptin and inhibits TCF-beta-catenin-mediated transcription. J Cell Sci. 118:3117–3129. 2005. View Article : Google Scholar : PubMed/NCBI

22 

Genovese G, Ghosh P, Li H, et al: The tumor suppressor HINT1 regulates MITF and beta-catenin transcriptional activity in melanoma cells. Cell Cycle. 11:2206–2215. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Wang L, Li H, Zhang Y, Santella RM and Weinstein IB: HINT1 inhibits beta-catenin/TCF4, USF2 and NFκB activity in human hepatoma cells. Int J Cancer. 124:1526–1534. 2009.PubMed/NCBI

24 

Yao H, Pan J, Qian Y, et al: Enhanced effect of soluble transforming growth factor-beta receptor II and IFN-gamma fusion protein in reversing hepatic fibrosis. Eur J Med Res. 15:152–161. 2010. View Article : Google Scholar : PubMed/NCBI

25 

Liu T and He YW: Protective effect of recombinant HMGB1 A box protein in mouse with acute hepatic failure. Zhonghua Gan Zang Bing Za Zhi. 18:222–226. 2010.(In Chinese).

26 

Schuppan D and Afdhal NH: Liver cirrhosis. Lancet. 371:838–851. 2008. View Article : Google Scholar : PubMed/NCBI

27 

Carpino G, Morini S, Ginanni Corradini S, et al: Alpha-SMA expression in hepatic stellate cells and quantitative analysis of hepatic fibrosis in cirrhosis and in recurrent chronic hepatitis after liver transplantation. Dig Liver Dis. 37:349–356. 2005. View Article : Google Scholar

28 

Safadi R and Friedman SL: Hepatic fibrosis-role of hepatic stellate cell activation. MedGenMed. 4:272002.PubMed/NCBI

29 

Shek FW and Benyon RC: How can transforming growth factor beta be targeted usefully to combat liver fibrosis? Eur J Gastroenterol Hepatol. 16:123–126. 2004. View Article : Google Scholar : PubMed/NCBI

30 

Cheon SS, Wei Q, Gurung A, et al: Beta-catenin regulates wound size and mediates the effect of TGF-beta in cutaneous healing. FASEB J. 20:692–701. 2006. View Article : Google Scholar : PubMed/NCBI

31 

Medici D, Hay ED and Olsen BR: Snail and Slug promote epithelial-mesenchymal transition through beta-catenin-T-cell factor-4-dependent expression of transforming growth factor-beta3. Mol Biol Cell. 19:4875–4887. 2008. View Article : Google Scholar : PubMed/NCBI

32 

Shtutman M, Zhurinsky J, Simcha I, et al: The cyclin D1 gene is a target of the beta-catenin/LEF-1 pathway. Proc Nat Acad Sci USA. 96:5522–5527. 1999. View Article : Google Scholar : PubMed/NCBI

33 

Razin E, Zhang ZC, Nechushtan H, et al: Suppression of microphthalmia transcriptional activity by its association with protein kinase C-interacting protein 1 in mast cells. J Biol Chem. 274:34272–34276. 1999. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wu F, Huang S, Zhu N, Liu W, Zhang Y and He Y: Recombinant human histidine triad nucleotide-binding protein 1 attenuates liver fibrosis induced by carbon tetrachloride in rats. Mol Med Rep 8: 1023-1028, 2013.
APA
Wu, F., Huang, S., Zhu, N., Liu, W., Zhang, Y., & He, Y. (2013). Recombinant human histidine triad nucleotide-binding protein 1 attenuates liver fibrosis induced by carbon tetrachloride in rats. Molecular Medicine Reports, 8, 1023-1028. https://doi.org/10.3892/mmr.2013.1618
MLA
Wu, F., Huang, S., Zhu, N., Liu, W., Zhang, Y., He, Y."Recombinant human histidine triad nucleotide-binding protein 1 attenuates liver fibrosis induced by carbon tetrachloride in rats". Molecular Medicine Reports 8.4 (2013): 1023-1028.
Chicago
Wu, F., Huang, S., Zhu, N., Liu, W., Zhang, Y., He, Y."Recombinant human histidine triad nucleotide-binding protein 1 attenuates liver fibrosis induced by carbon tetrachloride in rats". Molecular Medicine Reports 8, no. 4 (2013): 1023-1028. https://doi.org/10.3892/mmr.2013.1618
Copy and paste a formatted citation
x
Spandidos Publications style
Wu F, Huang S, Zhu N, Liu W, Zhang Y and He Y: Recombinant human histidine triad nucleotide-binding protein 1 attenuates liver fibrosis induced by carbon tetrachloride in rats. Mol Med Rep 8: 1023-1028, 2013.
APA
Wu, F., Huang, S., Zhu, N., Liu, W., Zhang, Y., & He, Y. (2013). Recombinant human histidine triad nucleotide-binding protein 1 attenuates liver fibrosis induced by carbon tetrachloride in rats. Molecular Medicine Reports, 8, 1023-1028. https://doi.org/10.3892/mmr.2013.1618
MLA
Wu, F., Huang, S., Zhu, N., Liu, W., Zhang, Y., He, Y."Recombinant human histidine triad nucleotide-binding protein 1 attenuates liver fibrosis induced by carbon tetrachloride in rats". Molecular Medicine Reports 8.4 (2013): 1023-1028.
Chicago
Wu, F., Huang, S., Zhu, N., Liu, W., Zhang, Y., He, Y."Recombinant human histidine triad nucleotide-binding protein 1 attenuates liver fibrosis induced by carbon tetrachloride in rats". Molecular Medicine Reports 8, no. 4 (2013): 1023-1028. https://doi.org/10.3892/mmr.2013.1618
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team