Platelet-derived growth factor-specific regulation of the JE promoter in rat aortic smooth muscle cells.
JE is a member of the family of "immediate early" genes induced by growth factors and cytokines. JE encodes a low molecular weight secretory glycoprotein analogous to the human monocyte chemoattractant protein, MCP-1. JE and MCP-1 proteins are thought to play an important role in inflammation and in the recruitment of monocyte/macrophages to the vessel wall during the development of atherosclerosis. We have previously reported that the induction of JE in rat aortic smooth muscle cells (SMC) was specific to platelet-derived growth factor (PDGF) and was not seen with other growth agonists. Using a luciferase reporter system and transient transfection assays of rat aortic SMC, we now report the identification of a region in the proximal rat JE promoter that is responsive to PDGF but not to other growth factors (angiotensin II and alpha-thrombin) or cytokines (interleukin 1-beta and tumor necrosis factor-alpha). The full response to PDGF (approximately 6-fold) requires the cooperative activity of two potentially novel cis-acting elements, at positions -146 to -128 and -84 to -59. While each element produces a different pattern in electrophoretic mobility shift assays, they appear to bind the same PDGF-responsive species. Further analysis of these regions should provide important insights into PDGF-specific responses in vascular SMC.
Bogdanov
V Y
VY
Cardiovascular Institute and Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.
Poon
M
M
Taubman
M B
MB
D000804:Angiotensin II; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000378:metabolism*; D000077214:Becaplermin; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D017781:Genes, Immediate-Early; D017930:Genes, Reporter; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007700:Kinetics; D008156:Luciferases / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology* / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000187:drug effects; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D013917:Thrombin / Q000494:pharmacology; D013997:Time Factors; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D018932:Chemokine CCL2; D007375:Interleukin-1; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; C075278:platelet-derived growth factor A; D000804:Angiotensin II; D000077214:Becaplermin; D008156:Luciferases; D013917:Thrombin