Arab Journal of Gastroenterology
Volume 10, Issue 4, Supplement , Pages S3-S6 , April 2010

Using a recombinant single chain antibody for targeting liver myofibroblasts with anti-fibrogenic therapeutics

  • Angela Douglass

      Affiliations

    • Institute of Cellular Medicine, University of Newcastle, UK
    • Wyeth Research, Polwarth Building, Foresterhill, Aberdeen, UK
    • School of Medical Sciences, University of Aberdeen, UK
    • ,
  • Karen Wallace

      Affiliations

    • Institute of Cellular Medicine, University of Newcastle, UK
    • ,
  • Matthew Koruth

      Affiliations

    • School of Medical Sciences, University of Aberdeen, UK
    • ,
  • Caroline Barelle

      Affiliations

    • Wyeth Research, Polwarth Building, Foresterhill, Aberdeen, UK
    • ,
  • Andrew J. Porter

      Affiliations

    • School of Medical Sciences, University of Aberdeen, UK
    • ,
  • Matthew C. Wright

      Affiliations

    • Institute of Cellular Medicine, University of Newcastle, UK
    • Corresponding Author InformationCorresponding author. Address: Institute of Cellular Medicine, School of Clinical and Laboratory Sciences, Level 2 William Leech Building, Medical School, Framlington Place, University of Newcastle, Upon Tyne NE2 4HH, UK.

References 

  1. Wallace K, Burt AD, Wright MC. Liver fibrosis. Biochem J. 2008;411:1–18
  2. Wright MC, Issa R, Smart DE, Trim N, Murray GI, Primrose JN, et al. Gliotoxin stimulates the apoptosis of human and rat hepatic stellate cells and enhances the resolution of liver fibrosis in rats. Gastroenterology. 2001;121:685–698
  3. Oakley F, Meso M, Iredale JP, Green K, Marek CJ, Zhou X, et al. Inhibition of inhibitor of kappaB kinases stimulates hepatic stellate cell apoptosis and accelerated recovery from rat liver fibrosis. Gastroenterology. 2005;128:108–120
  4. Hagens WI, Olinga P, Meijer DK, Groothuis GM, Beljaars L, Poelstra K. Gliotoxin non-selectively induces apoptosis in fibrotic and normal livers. Liver Int. 2006;26:232–239
  5. Dekel R, Zvibel I, Brill S, Brazovsky E, Halpern Z, Oren R. Gliotoxin ameliorates development of fibrosis and cirrhosis in a thioacetamide rat model. Dig Dis Sci. 2003;48:1642–1647
  6. Elrick LJ, Leel V, Blaylock MG, Duncan L, Drever MR, Strachan G, et al. Generation of a monoclonal human single chain antibody fragment to hepatic stellate cells – a potential mechanism for targeting liver anti-fibrotic therapeutics. J Hepatol. 2005;42:888–896
  7. Cassiman D, van Pelt J, De Vos R, Van Lommel F, Desmet V, Yap SH, et al. Synaptophysin: a novel marker for human and rat hepatic stellate cells. Am J Pathol. 1999;155:1831–1839
  8. McMahon HT, Bolshakov VY, Janz R, Hammer RE, Siegelbaum SA, Südhof TC. Synaptophysin, a major synaptic vesicle protein, is not essential for neurotransmitter release. Proc Natl Acad Sci USA. 1996;93:4760–4764
  9. Douglass A, Wallace K, Parr R, Park J, Durward E, Broadbent I, et al. Antibody-targeted myofibroblast apoptosis reduces fibrosis during sustained liver injury. J Hepatol. 2008;49:88–98
  10. Elsharkawy AM, Wright MC, Hay RT, Arthur MJ, Hughes T, Bahr MJ, et al. Persistent activation of nuclear factor-kappaB in cultured rat hepatic stellate cells involves the induction of potentially novel Rel-like factors and prolonged changes in the expression of IkappaB family proteins. Hepatology. 1999;30:761–769
  11. Orr JG, Leel V, Cameron GA, Marek CJ, Haughton EL, Elrick LJ, et al. Mechanism of action of the antifibrogenic compound gliotoxin in rat liver cells. Hepatology. 2004;40:232–242
  12. Anselmi K, Stolz DB, Nalesnik M, Watkins SC, Kamath R, Gandhi CR. Gliotoxin causes apoptosis and necrosis of rat Kupffer cells in vitro and in vivo in the absence of oxidative stress: exacerbation by caspase and serine protease inhibition. J Hepatol. 2007;47:103–113
  13. Duffield JS, Forbes SJ, Constandinou CM, Clay S, Partolina M, Vuthoori S, et al. Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair. J Clin Invest. 2005;115:56–65
  14. Rosenberg WM, et al. European Liver Fibrosis Group Serum markers detect the presence of liver fibrosis: a cohort study. Gastroenterology. 2004;127:1704–1713
  15. Rockey DC, Bissell DM. Noninvasive measures of liver fibrosis. Hepatology. 2006;43(2 Suppl. 1):S113–S120
  16. Fowell AJ, Iredale JP. Emerging therapies for liver fibrosis. Dig Dis. 2006;24:174–183
  17. Cortez-Pinto H, Camilo ME. Non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH): diagnosis and clinical course. Best Pract Res Clin Gastroenterol. 2004;18:1089–1104
  18. World Health Organisation. <http://www.who.int/mediacentre/factsheets/fs164/en/>.

PII: S1687-1979(09)00319-0

doi: 10.1016/j.ajg.2009.12.012

Arab Journal of Gastroenterology
Volume 10, Issue 4, Supplement , Pages S3-S6 , April 2010

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