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2010 | 15 | 2 |

Tytuł artykułu

A microarray gene analysis of peripheral whole blood in normal adult male rats after long-term GH gene therapy

Autorzy

Warianty tytułu

Języki publikacji

EN

Abstrakty

EN
The main aims of this study were to determine the effects of GH gene abuse/misuse in normal animals and to discover genes that could be used as candidate biomarkers for the detection of GH gene therapy abuse/misuse in humans. We determined the global gene expression profile of peripheral whole blood from normal adult male rats after long-term GH gene therapy using CapitalBio 27 K Rat Genome Oligo Arrays. Sixty one genes were found to be differentially expressed in GH gene-treated rats 24 weeks after receiving GH gene therapy, at a two-fold higher or lower level compared to the empty vector group (p < 0.05). These genes were mainly associated with angiogenesis, oncogenesis, apoptosis, immune networks, signaling pathways, general metabolism, type I diabetes mellitus, carbon fixation, cell adhesion molecules, and cytokine-cytokine receptor interaction. The results imply that exogenous GH gene expression in normal subjects is likely to induce cellular changes in the metabolism, signal pathways and immunity. A real-time qRT-PCR analysis of a selection of the genes confirmed the microarray data. Eight differently expressed genes were selected as candidate biomarkers from among these 61 genes. These 8 showed five-fold higher or lower expression levels after the GH gene transduction (p < 0.05). They were then validated in real-time PCR experiments using 15 single-treated blood samples and 10 control blood samples. In summary, we detected the gene expression profiles of rat peripheral whole blood after long-term GH gene therapy and screened eight genes as candidate biomarkers based on the microarray data. This will contribute to an increased mechanistic understanding of the effects of chronic GH gene therapy abuse/misuse in normal subjects.

Wydawca

-

Rocznik

Tom

15

Numer

2

Opis fizyczny

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Twórcy

autor
  • Chinese PLA General Hospital, 28 Fu-Xing Road, Beijing, 100853, P.R.China
autor

Bibliografia

  • 1. Götherström, G., Elbornsson, M., Stibrant-Sunnerhagen, K., Bengtsson, B.A., Johannsson, G. and Svensson J. Ten years of growth hormone (GH) replacement normalizes muscle strength in GH deficient adults. J. Clin. Endocrinol. Metab. 94 (2008) 809-816. DOI: 10.1210/jc.2008-1538.
  • 2. Ayuk, J. and Sheppard, M.C. Growth hormone and its disorders. Postgrad. Med. J. 82 (2006) 24-30. DOI: dx.doi.org/10.1136/pgmj.2005.036087.
  • 3. Rivera, V.M., Ye, X., Courage, N.L., Sachar, J., Cerasoli, F., Wilson, J.M. and Gilman, M. Long-term regulated expression of growth hormone in mice after intramuscular gene transfer. Proc. Natl. Acad. Sci. USA. 96 (1999) 8657-8662. DOI: dx.doi.org/10.1073/pnas.96.15.8657.
  • 4. Büning, H., Perabo, L., Coutelle, O., Quadt-Humme, S. and Hallek, M. Recent developments in adeno-associated virus vector technology. J. Gene Med. 10 (2008) 717-733. DOI: dx.doi.org/10.1002/jgm.1205.
  • 5. Filipp, F. Is science killing sport? Gene therapy and its possible abuse in doping. EMBO Rep. 8 (2007) 433-435. DOI: dx.doi.org/10.1038/ sj.embor. 7400968.
  • 6. Harridge, S.D. and Velloso, C.P. Gene doping. Essays Biochem. 44 (2007) 125-138. DOI: dx.doi.org/10.1042/BSE0440125.
  • 7. Melmed, S. Medical progress: Acromegaly. N. Engl. J. Med. 355 (2006) 2558-2573. DOI: dx.doi.org/10.1056/NEJMra062453.
  • 8. McCrory, P. Super athletes or gene cheats? Br. J. Sports Med. 37 (2003) 192-193. DOI: dx.doi.org/10.1136/bjsm.37.3.192.
  • 9. Wells, D.J. Gene doping: the hype and the reality. Br. J. Pharmacol. 154 (2008) 623-631. DOI: dx.doi.org/10.1038/bjp.2008.144.
  • 10. Schena, M., Shalon, D., Davis, R.W. and Brown, P.O. Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 270 (1995) 467-470. DOI: 10.1126/science.270. 5235.467.
  • 11. Chen, B.P., Li, Y.S., Zhao, Y., Chen, K.D., Li, S., Lao, J., Yuan, S., Shyy, J.Y. and Chien, S. DNA microarray analysis of gene expression in endothelial cells in response to 24-h shear stress. Physiol. Genomics 7 (2001) 55-63.
  • 12. Yan, H., Guo, Y.H., Zhang, P., Zu, L.Y., Dong, X.Y., Chen, L., Tian, J.W., Fan, X.L., Wang, N.P., Wu, X.B. and Gao, W. Superior neovascularization and muscle regeneration in ischemic skeletal muscles following VEGF gene transfer by rAAV1 pseudotyped vectors. Biochem. Biophys. Res. Commun. 336 (2005) 278-287. DOI: dx.doi.org/10.1016/j.bbrc.2005. 08.066.
  • 13. Snyder, R., Xiao, X. and Samulski, R.J. Production of recombinant adenoassociated viral vectors. in: Current Protocols in Human Genetics (Smith, D. Ed.), Wiley, New York, 1996, 12.1.1-12.2.23.
  • 14. Livak, K.J. and Schmittgen, T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods 25 (2001) 402-408. DOI: dx.doi.org/10.1006/meth.2001.1262.
  • 15. Herrington, J. and Carter-Su, C. Signaling pathways activated by the growth hormone receptor. Trends Endocrinol. Metab. 12 (2001) 252-257. DOI: dx.doi.org/10.1016/S1043-2760(01)00423-4.
  • 16. Lichanska, A.M. and Waters, M.J. How growth hormone controls growth, obesity and sexual dimorphism. Trends Genet. 24 (2007) 41-47. DOI: dx.doi.org/10.1016/j.tig.2007.10.006.
  • 17. Cormier, R.T., Hong, K.H., Halberg, R.B., Hawkins, T.L., Richardson, P., Mulherkar, R., Dove, W.F. and Lander, E.S. Secretory phospholipase Pla2g2a confers resistance to intestinal tumorigenesis. Nat. Genet. 17 (1997) 88-91. DOI: dx.doi.org/10.1038/ng0997-88.
  • 18. Kugiyama, K., Ota, Y., Sugiyama, S., Kawano, H., Doi, H., Soejima, H., Miyamoto, S., Ogawa, H., Takazoe, K. and Yasue, H. Prognostic value of plasma levels of secretory type II phospholipase A2 in patients with unstable angina pectoris. Am. J. Cardiol. 86 (2000) 718-722. DOI:10.1016/S0002- 9149(00)01069-9.
  • 19. Fijneman, R.J., Peham, J.R., van de Wiel, M.A., Meijer, G.A., Matise, I., Velcich, A. and Cormier, R.T. Expression of Pla2g2a prevents carcinogenesis in Muc2-deficient mice. Cancer Sci. 99 (2008) 2113-2119. DOI: dx.doi.org/10.1111/j.1349-7006.2008.00924.x.
  • 20. Hong, K.H., Bonventre, J.C., O’Leary, E., Bonventre, J.V. and Lander, E.S. Deletion of cytosolic phospholipase A (2) suppresses Apc(Min)-induced tumorigenesis. Proc. Natl. Acad. Sci. U.S.A. 98 (2001) 3935-3939. DOI: dx.doi.org/10.1073/pnas.051635898.
  • 21. Touqui, L. and Alaoui-El-Azher, M. Mammalian secreted phospholipases A2 and their pathophysiological significance in inflammatory diseases. Curr. Mol. Med. 1 (2001) 739-754. DOI: dx.doi.org/10.2174/ 1566524013363258.
  • 22. Pike, N.B. Flushing out the role of GPR109A (HM74A) in the clinical efficacy of nicotinic acid. J. Clin. Invest. 115 (2005) 3400-3403. DOI: dx.doi.org/10.1172/JCI27160.
  • 23. Martin, P.M., Ananth, S., Cresci, G., Roon, P., Smith, S. and Ganapathy, V. Expression and localization of GPR109A (PUMA-G/HM74A) mRNA and protein in mammalian retinal pigment epithelium. Mol. Vis. 15 (2009) 362-372.
  • 24. Chrzanowska-Wodnicka, M., Smyth, S.S., Schoenwaelder, S.M., Fischer, T.H. and White 2nd, G.C. Rap1b is required for normal platelet function and hemostasis in mice. J. Clin. Invest. 115 (2005) 680-687. DOI: 10.1172/ JCI22973.

Typ dokumentu

Bibliografia

Identyfikatory

Identyfikator YADDA

bwmeta1.element.agro-article-c212419f-4e34-4920-9112-a8093b570204
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