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
May-2016 Volume 13 Issue 5

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
May-2016 Volume 13 Issue 5

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 Open Access

Inhibition of the translocation and extracellular release of high-mobility group box 1 alleviates liver damage in fibrotic mice in response to D-galactosamine/lipopolysaccharide challenge

  • Authors:
    • Li Bai
    • Ming Kong
    • Qingfen Zheng
    • Xiaohui Zhang
    • Xin Liu
    • Kejia Zu
    • Yu Chen
    • Sujun Zheng
    • Junfeng Li
    • Feng Ren
    • Jinli Lou
    • Shuang Liu
    • Zhongping Duan
  • View Affiliations / Copyright

    Affiliations: Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, P.R. China, Clinical Laboratory Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, P.R. China, Department of Pathology, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, P.R. China, Research Department, Beijing Institute of Liver Diseases, Beijing 100069, P.R. China
    Copyright: © Bai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3835-3841
    |
    Published online on: March 18, 2016
       https://doi.org/10.3892/mmr.2016.5003
  • 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

Acute liver injury in the setting of fibrosis is an area of interest in investigations, and remains to be fully elucidated. Previous studies have suggested the beneficial effects of liver fibrosis induced by thioacetamide and partial bile duct ligation against Fas‑mediated acute liver injury. The activation of AKT and extracellular signal-regulated kinase signaling is considered to be crucial in this hepatoprotection. To demonstrate the protection of CCl4‑induced liver fibrosis against lethal challenge, the present study compared the reactivity to lethal doses of D‑galactosamine (D-GalN)/lipopolysaccharide (LPS) between fibrotic mice and control mice groups. The extent of hepatic damage was assessed by survival rate and histopathological analysis. The molecular basis of the fibrosis‑based hepatoprotection was examined, with a particular focus on the translocation and release of high‑mobility group box (HMGB)1 and the inflammatory response triggered by HMGB1. Hepatoprotection induced by fibrosis was demonstrated by improved survival rates (100%, vs. 20%) and improved preservation of liver architecture in fibrotic mice subjected to D‑GalN/LPS, compared with control mice treated in the same way. D‑GalN/LPS evoked the translocation and release of HMGB1, detected by immunohistochemistry, in the control mice, which was significantly inhibited in the fibrotic mice. The gene expression levels of HMGB1‑associated proinflammatory cytokines, including interleukin (IL)‑1β, IL‑6, tumor necrosis factor‑α and IL‑12p40, were markedly inhibited in the fibrotic mice when exposed to D‑GalN/LPS. These findings confirmed that CCl4‑based fibrosis induced hepatoprotection, and provided evidence that fibrosis inhibited the translocation and release of HMGB1, and the proinflammatory response triggered by HMGB1. This alleviated liver damage following exposure to D‑GalN/LPS challenge.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Friedman SL: Mechanisms of hepatic fibrogenesis. Gastroenterology. 134:1655–1669. 2008. View Article : Google Scholar : PubMed/NCBI

2 

Friedman SL: Evolving challenges in hepatic fibrosis. Nat Rev Gastroenterol Hepatol. 7:425–436. 2010. View Article : Google Scholar : PubMed/NCBI

3 

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

4 

White ES and Mantovani AR: Inflammation, wound repair and fibrosis: Reassessing the spectrum of tissue injury and resolution. J Pathol. 229:141–144. 2013. View Article : Google Scholar

5 

Wynn TA and Ramalingam TR: Mechanisms of fibrosis: Therapeutic translation for fibrotic disease. Nat Med. 18:1028–1040. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Osawa Y, Hannun YA, Proia RL and Brenner DA: Roles of AKT and sphingosine kinase in the antiapoptotic effects of bile duct ligation in mouse liver. Hepatology. 42:1320–1328. 2005. View Article : Google Scholar : PubMed/NCBI

7 

Bourbonnais E, Raymond VA, Ethier C, Nguyen BN, El-Leil MS, Meloche S and Bilodeau M: Liver fibrosis protects mice from acute hepatocellular injury. Gastroenterology. 142:130–139.e4. 2012. View Article : Google Scholar

8 

Javaherian K, Liu JF and Wang JC: Nonhistone proteins HMG1 and HMG2 change the DNA helical structure. Science. 199:1345–1346. 1978. View Article : Google Scholar : PubMed/NCBI

9 

Chen R, Hou W, Zhang Q, Kang R, Fan XG and Tang D: Emerging role of high-mobility group box 1 (HMGB1) in liver diseases. Mol Med. 19:357–366. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Li LC, Gao J and Li J: Emerging role of HMGB1 in fibrotic diseases. J Cell Mol Med. 18:2331–2339. 2014. View Article : Google Scholar : PubMed/NCBI

11 

Kang R, Chen R, Zhang Q, Hou W, Wu S, Cao L, Huang J, Yu Y, Fan XG, Yan Z, et al: HMGB1 in health and disease. Mol Aspects Med. 40:1–116. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Andersson U and Tracey KJ: HMGB1 is a therapeutic target for sterile inflammation and infection. Annu Rev Immunol. 29:139–162. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Huang H, Nace GW, McDonald KA, Tai S, Klune JR, Rosborough BR, Ding Q, Loughran P, Zhu X, Beer-Stolz D, et al: Hepatocyte-specific high-mobility group box 1 deletion worsens the injury in liver ischemia/reperfusion: A role for intracellular high-mobility group box 1 in cellular protection. Hepatology. 59:1984–1997. 2014. View Article : Google Scholar : PubMed/NCBI

14 

Kamo N, Ke B, Ghaffari AA, Shen XD, Busuttil RW, Cheng G and Kupiec-Weglinski JW: ASC/caspase-1/IL-1β signaling triggers inflammatory responses by promoting HMGB1 induction in liver ischemia/reperfusion injury. Hepatology. 58:351–362. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Sims GP, Rowe DC, Rietdijk ST, Herbst R and Coyle AJ: HMGB1 and RAGE in inflammation and cancer. Annu Rev Immunol. 28:367–388. 2010. View Article : Google Scholar : PubMed/NCBI

16 

Yanai H, Ban T, Wang Z, Choi MK, Kawamura T, Negishi H, Nakasato M, Lu Y, Hangai S, Koshiba R, et al: HMGB proteins function as universal sentinels for nucleic-acid-mediated innate immune responses. Nature. 462:99–103. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Albayrak A, Uyanik MH, Cerrah S, Altas S, Dursun H, Demir M and Uslu H: Is HMGB1 a new indirect marker for revealing fibrosis in chronic hepatitis and a new therapeutic target in treatment? Viral Immunol. 23:633–638. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Wang FP, Li L, Li J, Wang JY, Wang LY and Jiang W: High mobility group box-1 promotes the proliferation and migration of hepatic stellate cells via TLR4-dependent signal pathways of PI3K/Akt and JNK. PLoS One. 8:e643732013. View Article : Google Scholar : PubMed/NCBI

19 

Gong Q, Zhang H, Li JH, Duan LH, Zhong S, Kong XL, Zheng F, Tan Z, Xiong P, Chen G, et al: High-mobility group box 1 exacerbates concanavalin A-induced hepatic injury in mice. J Mol Med (Berl). 88:1289–1298. 2010. View Article : Google Scholar

20 

Zhou RR, Zhao SS, Zou MX, Zhang P, Zhang BX, Dai XH, Li N, Liu HB, Wang H and Fan XG: HMGB1 cytoplasmic translocation in patients with acute liver failure. BMC Gastroenterol. 11(21)2011. View Article : Google Scholar

21 

Kuroda N, Inoue K, Ikeda T, Hara Y, Wake K and Sato T: Apoptotic response through a high mobility box 1 protein-dependent mechanism in LPS/GalN-induced mouse liver failure and glycyrrhizin-mediated inhibition. PLoS One. 9:e928842014. View Article : Google Scholar : PubMed/NCBI

22 

Antoine DJ, Jenkins RE, Dear JW, Williams DP, McGill MR, Sharpe MR, Craig DG, Simpson KJ, Jaeschke H and Park BK: Molecular forms of HMGB1 and keratin-18 as mechanistic biomarkers for mode of cell death and prognosis during clinical acetaminophen hepatotoxicity. J Hepatol. 56:1070–1079. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Tsung A, Klune JR, Zhang X, Jeyabalan G, Cao Z, Peng X, Stolz DB, Geller DA, Rosengart MR and Billiar TR: HMGB1 release induced by liver ischemia involves toll-like receptor 4 dependent reactive oxygen species production and calcium-mediated signaling. J Exp Med. 204:2913–2923. 2007. View Article : Google Scholar : PubMed/NCBI

24 

National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals: Guide for the Care and Use of Laboratory Animals. 8th edition. National Academies Press; Washington (DC): 2011

25 

Lefkowitch JH: Pathologic diagnosis of liver disease. Hepatology - A Textbook of Liver Disease. Zakim D and Boyer TD: W.B. Saunders Company; Philadelphia: pp. 844–871. 1996

26 

Untergrasser A, Cutcutache I, Koressaar T, Ye J, Faircloth BC, Remm M and Rozen SG: Primer 3 - new capabilities and interfaces. Nucleic Acids Res. 40:e1152012. View Article : Google Scholar

27 

Dechêne A, Sowa JP, Gieseler RK, Jochum C, Bechmann LP, El Fouly A, Schlattjan M, Saner F, Baba HA, Paul A, et al: Acute liver failure is associated with elevated liver stiffness and hepatic stellate cell activation. Hepatology. 52:1008–1016. 2010. View Article : Google Scholar : PubMed/NCBI

28 

He Y, Jin L, Wang J, Yan Z, Chen T and Zhao Y: Mechanisms of fibrosis in acute liver failure. Liver Int. 35:1877–1885. 2015. View Article : Google Scholar

29 

Yang H, Hreggvidsdottir HS, Palmblad K, Wang H, Ochani M, Li J, Lu B, Chavan S, Rosas-Ballina M, Al-Abed Y, et al: A critical cysteine is required for HMGB1 binding to Toll-like receptor 4 and activation of macrophage cytokine release. Proc Natl Acad Sci USA. 107:11942–11947. 2010. View Article : Google Scholar : PubMed/NCBI

30 

Jung JH, Park JH, Jee MH, Keum SJ, Cho MS, Yoon SK and Jang SK: Hepatitis C virus infection is blocked by HMGB1 released from virus-infected cells. J Virol. 85:9359–9368. 2011. View Article : Google Scholar : PubMed/NCBI

31 

Youn JH and Shin JS: Nucleocytoplasmic shuttling of HMGB1 is regulated by phosphorylation that redirects it toward secretion. J Immunol. 177:7889–7897. 2006. View Article : Google Scholar : PubMed/NCBI

32 

Bonaldi T, Talamo F, Scaffidi P, Ferrera D, Porto A, Bachi A, Rubartelli A, Agresti A and Bianchi ME: Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion. EMBO J. 22:5551–5560. 2003. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Bai L, Kong M, Zheng Q, Zhang X, Liu X, Zu K, Chen Y, Zheng S, Li J, Ren F, Ren F, et al: Inhibition of the translocation and extracellular release of high-mobility group box 1 alleviates liver damage in fibrotic mice in response to D-galactosamine/lipopolysaccharide challenge. Mol Med Rep 13: 3835-3841, 2016.
APA
Bai, L., Kong, M., Zheng, Q., Zhang, X., Liu, X., Zu, K. ... Duan, Z. (2016). Inhibition of the translocation and extracellular release of high-mobility group box 1 alleviates liver damage in fibrotic mice in response to D-galactosamine/lipopolysaccharide challenge. Molecular Medicine Reports, 13, 3835-3841. https://doi.org/10.3892/mmr.2016.5003
MLA
Bai, L., Kong, M., Zheng, Q., Zhang, X., Liu, X., Zu, K., Chen, Y., Zheng, S., Li, J., Ren, F., Lou, J., Liu, S., Duan, Z."Inhibition of the translocation and extracellular release of high-mobility group box 1 alleviates liver damage in fibrotic mice in response to D-galactosamine/lipopolysaccharide challenge". Molecular Medicine Reports 13.5 (2016): 3835-3841.
Chicago
Bai, L., Kong, M., Zheng, Q., Zhang, X., Liu, X., Zu, K., Chen, Y., Zheng, S., Li, J., Ren, F., Lou, J., Liu, S., Duan, Z."Inhibition of the translocation and extracellular release of high-mobility group box 1 alleviates liver damage in fibrotic mice in response to D-galactosamine/lipopolysaccharide challenge". Molecular Medicine Reports 13, no. 5 (2016): 3835-3841. https://doi.org/10.3892/mmr.2016.5003
Copy and paste a formatted citation
x
Spandidos Publications style
Bai L, Kong M, Zheng Q, Zhang X, Liu X, Zu K, Chen Y, Zheng S, Li J, Ren F, Ren F, et al: Inhibition of the translocation and extracellular release of high-mobility group box 1 alleviates liver damage in fibrotic mice in response to D-galactosamine/lipopolysaccharide challenge. Mol Med Rep 13: 3835-3841, 2016.
APA
Bai, L., Kong, M., Zheng, Q., Zhang, X., Liu, X., Zu, K. ... Duan, Z. (2016). Inhibition of the translocation and extracellular release of high-mobility group box 1 alleviates liver damage in fibrotic mice in response to D-galactosamine/lipopolysaccharide challenge. Molecular Medicine Reports, 13, 3835-3841. https://doi.org/10.3892/mmr.2016.5003
MLA
Bai, L., Kong, M., Zheng, Q., Zhang, X., Liu, X., Zu, K., Chen, Y., Zheng, S., Li, J., Ren, F., Lou, J., Liu, S., Duan, Z."Inhibition of the translocation and extracellular release of high-mobility group box 1 alleviates liver damage in fibrotic mice in response to D-galactosamine/lipopolysaccharide challenge". Molecular Medicine Reports 13.5 (2016): 3835-3841.
Chicago
Bai, L., Kong, M., Zheng, Q., Zhang, X., Liu, X., Zu, K., Chen, Y., Zheng, S., Li, J., Ren, F., Lou, J., Liu, S., Duan, Z."Inhibition of the translocation and extracellular release of high-mobility group box 1 alleviates liver damage in fibrotic mice in response to D-galactosamine/lipopolysaccharide challenge". Molecular Medicine Reports 13, no. 5 (2016): 3835-3841. https://doi.org/10.3892/mmr.2016.5003
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