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Prepublished online as a Blood First Edition Paper on June 12, 2003; DOI 10.1182/blood-2003-01-0049. This Article Full Text (PDF) All Versions of this Article: 2003-01-0049v1 102/6/2115    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zhang, F. Articles by Rafii, S. Search for Related Content PubMed PubMed Citation Articles by Zhang, F. Articles by Rafii, S. Social Bookmarking                   What's this? Submitted January 22, 2003 Accepted May 16, 2003 Green fluorescent protein selectively induces HSP70-mediated upregulation of COX-2 expression in endothelial cells Fan Zhang, Neil R Hackett, George Lam, Joseph Cheng, Robert Pergolizzi, Lan Luo, Sergey Shmelkov, Jay Edelberg, Ronald G Crystal, and Shahin Rafii* Genetic Medicine, Weill Medical of Cornell University, New York, NY, USA Belfer Gene Therapy Core Facility, Weill Medical of Cornell University, New York, NY, USA Division of Hematology and Oncology, Weill Medical of Cornell University, New York, NY, USA Cardiology, Weill Medical of Cornell University, New York, NY, USA Genetic Medicine, Weill Medical of Cornell University, New York, NY, USA; Belfer Gene Therapy Core Facility, Weill Medical of Cornell University, New York, NY, USA Genetic Medicine, Weill Medical of Cornell University, New York, NY, USA; Division of Hematology and Oncology, Weill Medical of Cornell University, New York, NY, USA; Cardiology, Weill Medical of Cornell University, New York, NY, USA * Corresponding author; email: srafii{at}med.cornell.edu. Reporter genes, including green fluorescent protein (GFP), have been used to monitor the expression of transgenes introduced into vascular cells by gene transfer vectors. Here, we demonstrate that GFP by itself can selectively induce expression of certain genes in endothelial cells. Elevation of the cytoplasmic concentration of GFP in endothelial cells, specifically, resulted in a robust upregulation of heat shock protein 70 (HSP70). GFP induced both messenger RNA and protein expression of HSP70 in a dose-dependent manner. GFP-mediated upregulation of HSP70 resulted in induction of cyclooxygenase-2 (COX-2) followed by prostaglandin E2 (PGE2) production. GFP-mediated upregulation of HSP70 is independent of MAP-kinase and PI3-kinase signaling cascades as inhibition of these pathways had no effect upon HSP70 increases. Adenoviral delivery of GFP into murine vasculature significantly enhanced blood flow, suggesting that sufficient PGE2 is produced to induce vasodilation. Identification of the molecular partners that interact with GFP will increase our understanding of the vascular-specific factors that regulate stress angiogenesis and hemostasis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: U. Yokoyama, S. Minamisawa, H. Quan, T. Akaike, S. Suzuki, M. Jin, Q. Jiao, M. Watanabe, K. Otsu, S. Iwasaki, et al. Prostaglandin E2-activated Epac Promotes Neointimal Formation of the Rat Ductus Arteriosus by a Process Distinct from That of cAMP-dependent Protein Kinase A J. Biol. Chem., October 17, 2008; 283(42): 28702 - 28709. [Abstract] [Full Text] [PDF] S. Purhonen, J. Palm, D. Rossi, N. Kaskenpaa, I. Rajantie, S. Yla-Herttuala, K. Alitalo, I. L. Weissman, and P. Salven Bone marrow-derived circulating endothelial precursors do not contribute to vascular endothelium and are not needed for tumor growth PNAS, May 6, 2008; 105(18): 6620 - 6625. [Abstract] [Full Text] [PDF] G. C. Schatteman, M. Dunnwald, and C. Jiao Biology of bone marrow-derived endothelial cell precursors Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H1 - H18. [Abstract] [Full Text] [PDF] S. Rafii and D. Lyden Contribution of Hematopoietic and Vascular Progenitor Cells to the Neoangiogenic Niche Am. Assoc. Cancer Res. Educ. Book, April 1, 2006; 2006(1): 181 - 185. [Full Text] [PDF] F. Zhang, J. Cheng, G. Lam, D. K. Jin, L. Vincent, N. R. Hackett, S. Wang, L. M. Young, B. Hempstead, R. G. Crystal, et al. Adenovirus Vector E4 Gene Regulates Connexin 40 and 43 Expression in Endothelial Cells via PKA and PI3K Signal Pathways Circ. Res., May 13, 2005; 96(9): 950 - 957. [Abstract] [Full Text] [PDF] F. Zhang, J. Cheng, N. R. Hackett, G. Lam, K. Shido, R. Pergolizzi, D. K. Jin, R. G. Crystal, and S. Rafii Adenovirus E4 Gene Promotes Selective Endothelial Cell Survival and Angiogenesis via Activation of the Vascular Endothelial-Cadherin/Akt Signaling Pathway J. Biol. Chem., March 19, 2004; 279(12): 11760 - 11766. [Abstract] [Full Text] [PDF]

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