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Profiling of genes which are differentially expressed in mouse liver in response to adenoviral vectors and delivered genes

Abstract

The effects of transgene delivery by adenoviral vectors were studied by probing a 588 gene, mouse cDNA array with mRNA derived from infected liver. The liver tissues were obtained from naive mice and mice infected with replication-deficient adenovirus, adenovirus expressing transforming growth factor β1 (TGFβ1), and adenovirus expressing connective tissue growth factor (CTGF). Expression of 98 genes was detected in the array analysis. The increased expression of the transcripts for Stat1, gamma interferon-induced monokine (MIG) and interferon regulatory factor 1 (IRF1) clearly demonstrated the immune response induced by infection with a first generation, replication-incompetent adenovirus. In vivo expression of TGFβ1 led to a down-regulation of genes involved in the immune response. The increased expression of u-PAR1, laminin receptor and BMP-1 confirms the importance of CTGF and TGFβ1 in angiogenesis, and tissue repair. Expression of the serine protease inhibitors, Spi 2.4 and Spi 2, is also increased in response to AdTGFβ1 and AdCTGF.

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References

  1. Duggan DJ et al. Expression profiling using cDNA microarrays Nat Genet 1999 21: 10–14

    Article  CAS  Google Scholar 

  2. Shim C, Zhang W, Rhee CH, Lee JH . Profiling of differentially expressed genes in human primary cervical cancer by complementary DNA expression array Clin Cancer Res 1998 4: 3045–3050

    CAS  PubMed  Google Scholar 

  3. Sehgal A et al. Application of the differential hybridization of Atlas human expression arrays technique in the identification of differentially expressed genes in human glioblastoma multiforme tumor tissue J Surg Oncol 1998 67: 234–241

    Article  CAS  Google Scholar 

  4. Grande JP . Role of transforming growth factor-beta in tissue injury and repair Proc Soc Exp Biol Med 1997 214: 27–40

    Article  CAS  Google Scholar 

  5. Letterio JJ, Roberts AB . Regulation of immune responses by TGF-beta Annu Rev Immunol 1998 16: 137–161

    Article  CAS  Google Scholar 

  6. Terrell TG, Working PK, Chow CP, Green JD . Pathology of recombinant human transforming growth factor-beta 1 in rats and rabbits Int Rev Exp Pathol 1993 34: 43–67

    Article  Google Scholar 

  7. Grotendorst GR, Okochi H, Hayashi N . A novel transforming growth factor beta response element controls the expression of the connective tissue growth factor gene Cell Growth Diff 1996 7: 469–480

    CAS  PubMed  Google Scholar 

  8. Grotendorst GR . Connective tissue growth factor: a mediator of TGF-beta action on fibroblasts Cytokine Growth Factor Rev 1997 8: 171–179

    Article  CAS  Google Scholar 

  9. Ragot T, Opolon P, Perricaudet M . Adenoviral gene delivery Meth Cell Biol 1997 52: 229–260

    Article  CAS  Google Scholar 

  10. Yeh P, Perricaudet M . Advances in adenoviral vectors: from genetic engineering to their biology FASEB J 1997 11: 615–623

    Article  CAS  Google Scholar 

  11. Czarniecki CW et al. Transforming growth factor-beta 1 modulates the expression of class II histocompatibility antigens on human cells J Immunol 1988 140: 4217–4223

    CAS  PubMed  Google Scholar 

  12. Foster GR . Interferons in host defense Semin Liver Dis 1997 17: 287–295

    Article  CAS  Google Scholar 

  13. Wong P, Severns CW, Guyer NB, Wright TM . A unique palindromic element mediates gamma interferon induction of mig gene expression Mol Cell Biol 1994 14: 914–922

    Article  CAS  Google Scholar 

  14. Bammler TK, Smith CA, Wolf CR . Isolation and characterization of two mouse Pi-class glutathione S-transferase genes Biochem J 1994 298: 385–390

    Article  CAS  Google Scholar 

  15. Ram PA, Park SH, Choi HK, Waxman DJ . Growth hormone activation of Stat 1, Stat 3, and Stat 5 in rat liver. Differential kinetics of hormone desensitization and growth hormone stimulation of both tyrosine phosphorylation and serine/threonine phosphorylation J Biol Chem 1996 271: 5929–5940

    Article  CAS  Google Scholar 

  16. Akira S . Functional roles of STAT family proteins: lessons from knockout mice Stem Cells 1999 17: 138–146

    Article  CAS  Google Scholar 

  17. Mori T et al. Role and interaction of connective tissue growth factor with transforming growth factor-beta in persistent fibrosis: a mouse fibrosis model J Cell Physiol 1999 181: 153–159

    Article  CAS  Google Scholar 

  18. Brigstock DR . The connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed (CCN) family Endocr Rev 1999 20: 189–206

    CAS  PubMed  Google Scholar 

  19. Fajardo LF et al. Transforming growth factor beta1 induces angiogenesis in vivo with a threshold pattern Lab Invest 1996 74: 600–608

    CAS  PubMed  Google Scholar 

  20. Shimo T et al. Connective tissue growth factor induces the proliferation, migration, and tube formation of vascular endothelial cells in vitro, and angiogenesis in vivo J Biochem 1999 126: 137–145

    Article  CAS  Google Scholar 

  21. Kessler E et al. Bone morphogenetic protein-1: the type-I procollagen C-proteinase Science 1996 271: 360–362

    Article  CAS  Google Scholar 

  22. Lee S et al. Transforming growth factor-beta regulation of bone morphogenetic protein-1/procollagen C-proteinase and related proteins in fibrogenic cells and keratinocytes J Biol Chem 1997 272: 19059–19066

    Article  CAS  Google Scholar 

  23. Li H et al. Adenovirus-mediated delivery of a uPA/uPAR antagonist suppresses angiogenesis-dependent tumor growth and dissemination in mice Gene Therapy 1998 5: 1105–1113

    Article  CAS  Google Scholar 

  24. Shetty S et al. Differential expression of the urokinase receptor in fibroblasts from normal and fibrotic human lungs Am J Respir Cell Mol Biol 1996 15: 78–87

    Article  CAS  Google Scholar 

  25. Blasi F . The urokinase receptor. A cell surface, regulated chemokine APMIS 1999 107: 96–101

    Article  CAS  Google Scholar 

  26. Pages G et al. Molecular characterization of three rat liver serine-protease inhibitors affected by inflammation and hypophysectomy. Protein and mRNA analysis and cDNA cloning Eur J Biochem 1990 190: 385–391

    Article  CAS  Google Scholar 

  27. Ikeda T et al. Anti-invasive activity of synthetic serine protease inhibitors and its combined effect with a matrix metalloproteinase inhibitor Anticancer Res 1998 18: 4259–4265

    CAS  PubMed  Google Scholar 

  28. Roeb E et al. Regulation of tissue inhibitor of metalloproteinases-1 gene expression by cytokines and dexamethasone in rat hepatocyte primary cultures Hepatology 1993 18: 1437–1442

    Article  CAS  Google Scholar 

  29. Bett AJ, Haddara W, Prevec L, Graham FL . An efficient and flexible system for construction of adenovirus vectors with insertions or deletions in early regions 1 and 3 Proc Natl Acad Sci USA 1994 91: 8802–8806

    Article  CAS  Google Scholar 

  30. Fallaux FJ et al. Characterization of 911: a new helper cell line for the titration and propagation of early region 1-deleted adenoviral vectors Hum Gene Ther 1996 7: 215–222

    Article  CAS  Google Scholar 

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Acknowledgements

The authors thank Jeffrey Greve and Michael Eckart for their excellent advice and review of the manuscript.

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Haberberger, T., Kupfer, K. & Murphy, J. Profiling of genes which are differentially expressed in mouse liver in response to adenoviral vectors and delivered genes. Gene Ther 7, 903–909 (2000). https://doi.org/10.1038/sj.gt.3301181

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