Platelet-derived growth factor specifically induced an approximately 6-fold response in the proximal rat JE promoter in aortic smooth muscle cells, requiring two novel cis-acting elements.
The study identifies specific cis-acting elements in the JE promoter that mediate PDGF-specific gene induction in vascular smooth muscle cells, providing molecular insights into mechanisms relevant to atherosclerosis.
Effect estimate: approximately 6-fold
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 et al. (Tue,) reported a other. Platelet-derived growth factor (PDGF) vs. Other growth factors and cytokines was evaluated on JE promoter response (approximately 6-fold). Platelet-derived growth factor specifically induced an approximately 6-fold response in the proximal rat JE promoter in aortic smooth muscle cells, requiring two novel cis-acting elements.