Pulmonary expression of early growth response-1: biphasic time course and effect of oxygen concentration

Hypoxia induces complex adaptive responses. In this report, induction of ea rly growth response-1 (Egr-1) transcripts in lungs of mice subjected to hyp oxia is shown to be dose and time dependent. Within 30 min of hypoxia, Egr- 1 transcripts were similar to 20-fold elevated in 6% oxygen, similar to 5.2 -fold increased by 10% oxygen, and returned to the normoxic baseline by 12% oxygen. Time course studies up to 48 h showed a biphasic profile with an i nitial steep rise in Egr-1 transcripts after 0.5 h of hypoxia and a second elevation beginning after 20-24 h. Hypoxic induction of Egr-1 was parallele d by enhanced expression of the downstream target gene tissue factor. Egr-1 and tissue factor antigen were visualized in bronchial and vascular smooth muscle and in alveolar macrophages. Egr-1 has the capacity to modulate exp ression of genes involved in the remodeling of the extracellular matrix and properties of smooth muscle, thus possibly contributing to the pulmonary r esponse to chronic hypoxia.