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Analysis of Proteins and Genes Dominantly Expressed in Stellate Cells of Activated Phenotype: the Molecular Approach to Liver Fibrosis

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Liver Cirrhosis
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Summary

The stellate cell is a principal producer of extracellular matrix proteins in the liver and plays a major role in the development of liver fibrosis. The molecular basis of cell activation has therefore been intensively analyzed during the past decade. In order to reveal the total gene/protein synthesis in stellate cells, in particular the dynamic change in their level of expression in response to activation, suppression subtractive hybridization and proteomics/genomics analysis were performed. In suppression subtractive hybridization, 11 genes dominantly expressed in activated stellate cells were identified. One of them was cellular prion protein, whose expression was clearly restricted to activated stellate cells also in the in vivo fibrosis model. Over 150 stellate cell genes/proteins were successfully analyzed by proteomics/genomics, and several of them, including novel observations, represent activation-associated change. Thus, molecules associated with stellate cell activation and consequently liver fibrosis may remain undiscovered. Comprehensive understanding of the molecular basis of liver fibrosis is required.

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References

  1. Blomhoff R, Wake K (1991) Perisinusoidal stellate cells of the liver: important roles in retinol metabolism and fibrosis. FASEB J 5: 271–277

    PubMed  CAS  Google Scholar 

  2. Friedman SL (1993) The cellular basis of hepatic fibrosis. N Engl J Med 328: 1828–1835

    Article  PubMed  CAS  Google Scholar 

  3. Gressner AM, Bachem MG (1995) Molecular mechanism of liver fibrosis: a homage to the role of activated fat-storing cells. Digestion 56: 335–346

    Article  PubMed  CAS  Google Scholar 

  4. Olaso E, Friedman SL (1998) Molecular regulation of hepatic fibrogenesis. J Hepatol 29: 836–847

    Article  PubMed  CAS  Google Scholar 

  5. Kawada N (1997) The hepatic perisinusoidal stellate cell. Histol Histopathol 12: 1069–1080

    PubMed  CAS  Google Scholar 

  6. Kim Y, Ratziu V, Choi SG, Lalazar A, Theiss G, Dang Q, Kim SJ, Friedman SL (1998) Transcriptional activation of transforming growth factor beta, and its receptors by the Kruppel-like factor Zf9/core promoter-binding protein and Sp l: potential mechanisms for autocrine fibrogenesis in response to injury. J Biol Chem 273: 33750–33758

    Article  PubMed  CAS  Google Scholar 

  7. Marra F, Gentilini A, Pinzani M, Choudhury GG, Parola M, Herbst H, Dianzani MU, Laffi G, Abboud HE, Gentilini P (1997) Phosphatidylinositol 3-kinase is required for platelet-derived growth factor’s actions on hepatic stellate cells. Gastroenterology 112: 1297–1306

    Article  PubMed  CAS  Google Scholar 

  8. Kawada N, Ikeda K, Seki S, Kuroki T (1999) Expression of cyclins D1, D2 and E correlates with proliferation of rat stellate cells in culture. J Hepatol 30: 1057–1064

    Google Scholar 

  9. Hellerbrand C, Stefanovic B, Giordano F, Burchardt ER, Brenner DA (1999) The role of TGF beta, in initiating hepatic stellate cell activation in vivo. J Hepatol 30: 77–87

    Article  PubMed  CAS  Google Scholar 

  10. George J, Roulot D, Koteliansky VE, Bissell DM (1999) In vivo inhibition of rat stellate cell activation by soluble transforming growth factor beta type II receptor: a potential new therapy for hepatic fibrosis. Proc Natl Acad Sci USA 96: 12719–12724

    Article  PubMed  CAS  Google Scholar 

  11. Kawada N, Tran-Thi TA, Klein H, Decker K (1993) The contraction of hepatic stellate (Ito) cells stimulated with vasoactive substances: possible involvement of endothelin 1 and nitric oxide in the regulation of the sinusoidal tonus. Eur J Biochem 213: 815–823

    Article  PubMed  CAS  Google Scholar 

  12. Rockey DC, Weisiger RA (1996) Endothelin induced contractility of stellate cells from normal and cirrhotic rat liver: implications for regulation of portal pressure and resistance. Hepatology 24: 233–240

    Article  PubMed  CAS  Google Scholar 

  13. Diatchenko L, Lau YF, Campbell AP, Chenchik A, Moqadam F, Huang B, Lukyanov S, Lukyanov K, Gurskaya N, Sverdlov ED, Siebert PD (1996) Suppression subtractive

    Google Scholar 

  14. hybridization: a method for generating differentially regulated or tissue-specific cDNA probes and libraries. Proc Natl Acad Sci USA 93:6025–6030

    Google Scholar 

  15. Diatchenko L, Lukyanov S, Lau YF, Siebert PD (1999) Suppression subtractive hybridization: a versatile method for identifying differentially expressed genes. Methods Enzymol 303: 349–380

    Article  PubMed  CAS  Google Scholar 

  16. Ikeda K, Kawada N, Wang YQ, Kadoya H, Nakatani K, Sato M, Kaneda K (1998) Expression of cellular prion protein in activated hepatic stellate cells. Am J Pathol 153: 1695–1700

    Article  PubMed  CAS  Google Scholar 

  17. Knittel T, Aurisch S, Neubauer K, Eichhorst S, Ramadori G (1996) Cell-type-specific expression of neural cell adhesion molecule (N-CAM) in Ito cells of rat liver. Up-regulation during in vitro activation and in hepatic tissue repair. Am J Pathol 149: 449–462

    Google Scholar 

  18. Niki T, Pekny M, Hellemans K, Bleser PD, Berg KV, Vaeyens F, Quartier E, Schuit F, Geerts A (1999) Class VI intermediate filament protein nestin is induced during activation of rat hepatic stellate cells. Hepatology 29: 520–527

    Article  PubMed  CAS  Google Scholar 

  19. Kahn P (1995) From genome to proteome: looking at a cell’s proteins. Science 270: 369–370

    Article  PubMed  CAS  Google Scholar 

  20. Anderson NL, Anderson NG (1998) Proteome and proteomics: new technologies, new concepts, and new words. Electrophoresis 19: 1853–1861

    Article  PubMed  CAS  Google Scholar 

  21. Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O’Brien KP, et al. (1999) The DNA sequence of human chromosome 22. Nature 402: 489–495

    Article  PubMed  CAS  Google Scholar 

  22. O’Farrell PH (1975) High resolution two-dimensional electrophoresis of proteins. J Biol Chem 250: 4007–4021

    PubMed  Google Scholar 

  23. Roepstorff P (1997) Mass spectrometry on protein studies from genome to function. Curr Opin Biotechnol 8: 6–13

    Article  PubMed  CAS  Google Scholar 

  24. Yates JR (1998) Mass spectrometry and the age of the proteome. J Mass Spectrom 33: 1–19

    Article  PubMed  CAS  Google Scholar 

  25. Schena M, Shalon D, Davis RW, Brown PO (1995) Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 270: 467–470

    Article  PubMed  CAS  Google Scholar 

  26. DeRisi J, Penland L, Brown PO, Bittner ML, Meltzer PS, Ray M, Chen Y, Su YA, Trent JM (1996) Use of a cDNA microarray to analyse gene expression patterns in human cancer. Nature Genet 14: 457–460

    Article  PubMed  CAS  Google Scholar 

  27. Liang P, Pardee AB (1992) Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction. Science 257: 967–971

    Article  PubMed  CAS  Google Scholar 

  28. Ito T, Sakaki Y (1999) Fluorescent differential display: a fast and reliable method for message display polymerase chain reaction. Methods Enzymol 303: 298–309

    Article  PubMed  CAS  Google Scholar 

  29. Velculescu VE, Zhang L, Vogelstein B, Kinzler KW (1995) Serial analysis of gene expression. Science 270: 484–487

    Article  PubMed  CAS  Google Scholar 

  30. Afshari CA, Nuwaysir EF, Barrett JC (1999) Application of complementary DNA microarray technology to carcinogen identification, toxicology, and drug safety evaluation. Cancer Res 59: 4759–4760

    PubMed  CAS  Google Scholar 

  31. Bryant Z, Subrahmanyan L, Tworoger M, LaTray L, Liu CR, Li MJ, van den Engh G, Ruohola-Baker H (1999) Characterization of differentially expressed genes in purified Drosophila follicle cells: toward a general strategy for cell type-specific developmental analysis. Proc Natl Acad Sci USA 96: 5559–5564

    Article  PubMed  CAS  Google Scholar 

  32. Gong W, Pecci A, Roth S, Lahme B, Beato M, Gressner AM (1998) Transformation-dependent susceptibility of rat hepatic stellate cells to apoptosis induced by soluble Fas ligand. Hepatology 28: 492–502

    Article  PubMed  CAS  Google Scholar 

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© 2001 Springer-Verlag Tokyo

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Kawada, N. (2001). Analysis of Proteins and Genes Dominantly Expressed in Stellate Cells of Activated Phenotype: the Molecular Approach to Liver Fibrosis. In: Okita, K. (eds) Liver Cirrhosis. Springer, Tokyo. https://doi.org/10.1007/978-4-431-68343-8_2

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  • DOI: https://doi.org/10.1007/978-4-431-68343-8_2

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-68345-2

  • Online ISBN: 978-4-431-68343-8

  • eBook Packages: Springer Book Archive

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