Green fluorescent protein selectively induces HSP70-mediated up-regulation of COX-2 expression in endothelial cells

Fan Zhang, Neil R. Hackett, George Lam, Joseph Cheng, Robert Pergolizzi, Lan Luo, Sergey V. Shmelkov, Jay Edelberg, Ronald Crystal, Shahin Rafii

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

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 up-regulation of heat shock protein 70 (HSP70). GFP induced both mRNA and protein expression of HSP70 in a dose-dependent manner. GFP-mediated up-regulation of HSP70 resulted in induction of cyclooxygenase-2 (COX-2) followed by prostaglandin E2 (PGE2) production. GFP-mediated up-regulation of HSP70 is independent of mitogen-activated protein kinase and phosphatidylinositol-3-kinase signaling cascades because inhibition of these pathways had no effect on 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.

Original languageEnglish
Pages (from-to)2115-2121
Number of pages7
JournalBlood
Volume102
Issue number6
DOIs
Publication statusPublished - 15 Sep 2003
Externally publishedYes

Fingerprint

HSP70 Heat-Shock Proteins
Endothelial cells
Cyclooxygenase 2
Green Fluorescent Proteins
Up-Regulation
Endothelial Cells
Dinoprostone
Genes
Phosphatidylinositol 3-Kinase
Gene transfer
Mitogen-Activated Protein Kinases
Hemostasis
Transgenes
Reporter Genes
Vasodilation
Blood Vessels
Blood
Gene Expression
Messenger RNA

ASJC Scopus subject areas

  • Immunology
  • Biochemistry
  • Hematology
  • Cell Biology

Cite this

Zhang, F., Hackett, N. R., Lam, G., Cheng, J., Pergolizzi, R., Luo, L., ... Rafii, S. (2003). Green fluorescent protein selectively induces HSP70-mediated up-regulation of COX-2 expression in endothelial cells. Blood, 102(6), 2115-2121. https://doi.org/10.1182/blood-2003-01-0049

Green fluorescent protein selectively induces HSP70-mediated up-regulation of COX-2 expression in endothelial cells. / Zhang, Fan; Hackett, Neil R.; Lam, George; Cheng, Joseph; Pergolizzi, Robert; Luo, Lan; Shmelkov, Sergey V.; Edelberg, Jay; Crystal, Ronald; Rafii, Shahin.

In: Blood, Vol. 102, No. 6, 15.09.2003, p. 2115-2121.

Research output: Contribution to journalArticle

Zhang, F, Hackett, NR, Lam, G, Cheng, J, Pergolizzi, R, Luo, L, Shmelkov, SV, Edelberg, J, Crystal, R & Rafii, S 2003, 'Green fluorescent protein selectively induces HSP70-mediated up-regulation of COX-2 expression in endothelial cells', Blood, vol. 102, no. 6, pp. 2115-2121. https://doi.org/10.1182/blood-2003-01-0049
Zhang, Fan ; Hackett, Neil R. ; Lam, George ; Cheng, Joseph ; Pergolizzi, Robert ; Luo, Lan ; Shmelkov, Sergey V. ; Edelberg, Jay ; Crystal, Ronald ; Rafii, Shahin. / Green fluorescent protein selectively induces HSP70-mediated up-regulation of COX-2 expression in endothelial cells. In: Blood. 2003 ; Vol. 102, No. 6. pp. 2115-2121.
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