This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 23/6/988    most recent 01.ATV.0000071351.07784.19v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hasan, R. N. Articles by Harada, S. Search for Related Content PubMed PubMed Citation Articles by Hasan, R. N. Articles by Harada, S. Related Collections Cell signalling/signal transduction Gene expression Type 2 diabetes Mechanism of atherosclerosis/growth factors

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:988.)
© 2003 American Heart Association, Inc.

Vascular Biology

Differential Regulation of Early Growth Response Gene-1 Expression by Insulin and Glucose in Vascular Endothelial Cells

Rukhsana N. Hasan; Sharbani Phukan; Shuko Harada

From the Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pa.

Correspondence to Shuko Harada, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 218 John Morgan Building, 37th and Hamilton Walk, Philadelphia, PA 19104. E-mail haradas{at}mail.med.upenn.edu

Objective— Early growth response gene (Egr)-1 is a key transcription factor involved in vascular pathophysiology. Its role in diabetic vascular complications, however, remains unclear. Because hyperinsulinemia and hyperglycemia are major risk factors leading to diabetic vascular complications, we examined the effect of insulin and glucose on Egr-1 expression in murine glomerular vascular endothelial cells.

Methods and Results— Insulin or glucose, when added separately, increased egr-1 mRNA levels and promoter activity, as well as Egr-1 protein levels in nuclear extracts. When insulin was added to cells preincubated with glucose, the two had an additive effect on Egr-1 expression. Furthermore, vascular endothelial growth factor receptor-1 (flt-1) and plasminogen activator inhibitor-1, two known Egr-1-responsive genes, were also upregulated in the presence of insulin or glucose. An investigation into the underlying molecular mechanisms demonstrated that insulin, but not glucose, increased Egr-1 expression through extracellular signal-regulated kinase 1/2 activation, which is consistent with our previous reports. In contrast, inhibition of protein kinase C by phorbol ester or by the specific protein kinase C inhibitor chelerythrine chloride downregulated glucose-induced, but not insulin-induced, Egr-1 expression.

Conclusions— Differential regulation of Egr-1 expression by insulin and glucose in vascular cells may be one of the initial key events that plays a crucial role in the development of diabetic vascular complications.

Key Words: Egr-1 • vascular endothelial cells • insulin • mitogen-activated protein kinase • protein kinase C

This article has been cited by other articles:

				L. Zhu, C. Johnson, and M. Bakovic Stimulation of the human CTP:phosphoethanolamine cytidylyltransferase gene by early growth response protein 1 J. Lipid Res., October 1, 2008; 49(10): 2197 - 2211. [Abstract] [Full Text] [PDF]

				P. Dabir, T. E. Marinic, I. Krukovets, and O. I. Stenina Aryl Hydrocarbon Receptor Is Activated by Glucose and Regulates the Thrombospondin-1 Gene Promoter in Endothelial Cells Circ. Res., June 20, 2008; 102(12): 1558 - 1565. [Abstract] [Full Text] [PDF]

				D. Onat, S. Jelic, A. M. Schmidt, J. Pile-Spellman, S. Homma, M. Padeletti, Z. Jin, T. H. Le Jemtel, P. C. Colombo, and L. Feng Vascular endothelial sampling and analysis of gene transcripts: a new quantitative approach to monitor vascular inflammation J Appl Physiol, November 1, 2007; 103(5): 1873 - 1878. [Abstract] [Full Text] [PDF]

				E. Bertrand, C. Fritsch, S. Diether, G. Lambrou, D. Muller, F. Schaeffel, P. Schindler, K. L. Schmid, J. van Oostrum, and H. Voshol Identification of Apolipoprotein A-I as a "STOP" Signal for Myopia Mol. Cell. Proteomics, November 1, 2006; 5(11): 2158 - 2166. [Abstract] [Full Text] [PDF]

				K. Eto, V. Kaur, and M. K. Thomas Regulation of Insulin Gene Transcription by the Immediate-Early Growth Response Gene Egr-1 Endocrinology, June 1, 2006; 147(6): 2923 - 2935. [Abstract] [Full Text] [PDF]

				S.-Q. Wu and W. C. Aird Thrombin, TNF-{alpha}, and LPS exert overlapping but nonidentical effects on gene expression in endothelial cells and vascular smooth muscle cells Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H873 - H885. [Abstract] [Full Text] [PDF]

				Y. Takahashi, L. Li, M. Kamiryo, T. Asteriou, A. Moustakas, H. Yamashita, and P. Heldin Hyaluronan Fragments Induce Endothelial Cell Differentiation in a CD44- and CXCL1/GRO1-dependent Manner J. Biol. Chem., June 24, 2005; 280(25): 24195 - 24204. [Abstract] [Full Text] [PDF]