Phenotypic Changes Consequent on Egr1 Induction

Egr-1 up-regulates the expression of plasminogen activator inhibitor-1 (PAI-1) and TF (Houston et al. 1999). Concomitantly, the tissue plasminogen activator (tPA) is down-regulated; the receptors for tPA are proteoglycans on the EC surface. These changes tend towards fibrin production (Pinsky et al. 1998). Egr-1 also activates the transcription of genes associated with stress, including those that encode TNF-a, ICAM-1,2 CD44, PDGF, transforming growth factor-P(TGF-P), IL-1p and macrophage colony stimulating factor (M-CSF) (Yan et al. 2000a). Other examples include metalloproteinases that modify the subendothelial ECM, with possible implications for blood coagulation and leukocyte migration (Haas et al. 1999). Egr-1 also mediates the induction of PDGF synthesis by EC exposed to fibroblast growth factor-1 (FGF-1) (Delbridge and Khachigian 1997). It is uncertain whether it is involved in the numerous responses of macrophages to hypoxia (increased metabolic activity and phagocytosis, altered morphology and cell surface markers and cytokine production) (Lewis et al. 1999), but it seems to be implicated in macrophage line differentiation (Nguyen et al. 1993). Interestingly, Egr-1 induces the formation of reactive oxygen species (ROS) in some cell lines (Bek et al. 2003). Some of these details are summarised in Fig. 12.2.

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