Beregovyi S. The role of transcriptional factor Egr-1 in pathogenesis of ulcer disease

The results showed that the redox-sensitive transcription factors Egr-1 and Sp-1 enter into competitive interactions in the early stages of stress and aspirin-induced gastric lesions in rats. The level of protein and mRNA Egr-1 increases opposite - the level of Sp-1 decreases. Under the conditions of ethanol-induced ulcers, the level of Egr-1 does not change, but Sp-1 - increases. The development of erosive and ulcerative lessions in the gastric mucosa of rats caused by stress, aspirin and ethanol resulted in multidirectional changes in the level of protein VEGF and bFGF. Increasing the level VEGF is a characteristic sign of development gastric lesions during stress, aspirin and ethanol action. bFGF level gradually increased on the background of stress and aspirin-induced gastric lesions and vice versa decreased during ethanol action. Development of erosive and ulcerative lesions in the stomach during stress action was accompanied by a decrease in the partial pressure of oxygen in the cells of the gastric mucous membrane, and caused increasing in the level of transcription factor response to hypoxia HIF-1alpha and reducing protein SH-groups, that can be indication of changes in tissue redox status and may be indirect evidence of activation of redox-sensitive transcription factor Egr-1. In the early stages of stress-induced gastric lesions increased concentrations of the stress hormone cortisol in serum is associated with activation of Erk1/2 MAP-kinase pathway and does not affect p38. Inhibition of Erk1/2 by the selective inhibitor PD98059 lead to more aggressive lesions of the stomach accompanied by a reduction in Egr-1, and accordingly, pro-angiogenic factors VEGF and bFGF.