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Blood, 15 February 2004, Vol. 103, No. 4, pp. 1319-1324. Prepublished online as a Blood First Edition Paper on October 30, 2003; DOI 10.1182/blood-2003-04-1015. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-04-1015v1 103/4/1319    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Al-Nedawi, K. N. I. Articles by Cierniewski, C. S. Search for Related Content PubMed PubMed Citation Articles by Al-Nedawi, K. N. I. Articles by Cierniewski, C. S. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cytoskeleton Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Thymosin 4 induces the synthesis of plasminogen activator inhibitor 1 in cultured endothelial cells and increases its extracellular expression Khalid N. I. Al-Nedawi, Malgorzata Czyz, Radoslaw Bednarek, Janusz Szemraj, Maria Swiatkowska, Aleksandra Cierniewska-Cieslak, Janina Wyczolkowska, and Czeslaw S. Cierniewski From the Center for Medical Biology and Microbiology, Polish Academy of Sciences, Lodz, Poland; and Departments of Medicinal Chemistry, Biochemistry, and Molecular and Medical Biophysics, Medical University in Lodz, Lodz, Poland. Thymosin 4(T4), a 4.9-kDa polypeptide primarily known as a main G-actin–sequestering peptide, is present in high concentrations in various cells and in the circulation. We have found that T4 upregulates the expression of plasminogen activator inhibitor 1 (PAI-1) in endothelial cells measured both at the level of mRNA and protein synthesis. This effect seems to be cell specific and was not observed when other cells such as human fibroblasts, PC3, and U937 were tested. T4 significantly activated the PAI-1 promoter in EA.hy 926 cells transiently transfected either with plasmid p800LUC containing PAI-1 promoter fragment (–800 to +71) or the PAI-1 promoter linked with green fluorescent protein. T4 mediated up-regulation of PAI-1 involved activation of the mitogen-activated protein kinase cascade. Furthermore, T4 enhanced c-Fos/c-Jun DNA-binding activity to the activator protein 1 (AP-1)–like element (–59 to –52). The specificity of this binding activity was demonstrated by competition electrophoretic mobility shift assay and after transfection of EA.hy 926 cells with the mutated PAI-1 promoter. Taken together, these data indicate that, in response to T4 stimulation, AP-1 activity increases to enhance PAI-1 transcription through its unique AP-1–like element at –59 to –52 in the PAI-1 promoter. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J H-C Ho, K-C Tseng, W-H Ma, K-H Chen, O K-S Lee, and Y Su Thymosin beta-4 upregulates anti-oxidative enzymes and protects human cornea epithelial cells against oxidative damage Br J Ophthalmol, July 1, 2008; 92(7): 992 - 997. [Abstract] [Full Text] [PDF] R. Bednarek, J. Boncela, K. Smolarczyk, A. Cierniewska-Cieslak, E. Wyroba, and C. S. Cierniewski Ku80 as a Novel Receptor for Thymosin 4 That Mediates Its Intracellular Activity Different from G-actin Sequestering J. Biol. Chem., January 18, 2008; 283(3): 1534 - 1544. [Abstract] [Full Text] [PDF] J. H.-C. Ho, C.-H. Chuang, C.-Y. Ho, Y.-R. V. Shih, O. K.-S. Lee, and Y. Su Internalization Is Essential for the Antiapoptotic Effects of Exogenous Thymosin {beta}-4 on Human Corneal Epithelial Cells Invest. Ophthalmol. Vis. Sci., January 1, 2007; 48(1): 27 - 33. [Abstract] [Full Text] [PDF] A. A. Eddy and A. B. Fogo Plasminogen Activator Inhibitor-1 in Chronic Kidney Disease: Evidence and Mechanisms of Action J. Am. Soc. Nephrol., November 1, 2006; 17(11): 2999 - 3012. [Full Text] [PDF] J. Boncela, K. Smolarczyk, E. Wyroba, and C. S. Cierniewski Binding of PAI-1 to Endothelial Cells Stimulated by Thymosin beta4 and Modulation of Their Fibrinolytic Potential J. Biol. Chem., January 13, 2006; 281(2): 1066 - 1072. [Abstract] [Full Text] [PDF] B. J. Xu, Y. Shyr, X. Liang, L.-j. Ma, E. M. Donnert, J. D. Roberts, X. Zhang, V. Kon, N. J. Brown, R. M. Caprioli, et al. Proteomic Patterns and Prediction of Glomerulosclerosis and Its Mechanisms J. Am. Soc. Nephrol., October 1, 2005; 16(10): 2967 - 2975. [Abstract] [Full Text] [PDF]

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