REDOX-SENSITIVE TRANSCRIPTION FACTORS EGR-1 AND SP1 IN THE PATHOGENESIS OF EXPERIMENTAL GASTRIC ULCER

Area of Science:

• Cellular and Molecular Biology
• Gastroenterology
• Biochemistry

Background:

• Gastric mucosal redox status changes are key in gastric erosion and ulcer development.
• Redox-sensitive transcription factors, like Egr-1 and Sp-1, may influence genes critical for gastric ulcer pathogenesis.
• These factors regulate genes involved in growth factors and cell cycle, impacting ulcer formation.

Purpose of the Study:

• To investigate the role of zinc-finger transcription factors Egr-1 and Sp-1 in the molecular mechanisms of aspirin-induced and stress-induced gastric lesions.
• To elucidate the involvement of these transcription factors in the early stages of gastric ulcer development.

Main Methods:

• Gastric ulcers were induced in rats using immobilization stress with water-immersion (IMO-WI) or aspirin gavage.
• Rats were euthanized at 20 minutes, 1 hour, and 3 hours post-induction.
• Protein expression (Western blot), mRNA levels (RT-PCR), and protein SH-groups (Ellman's method) were analyzed.

Main Results:

• Gastric ulcer development correlated with a significant decrease in protein SH-groups in the gastric mucosa.
• A significant increase in Egr-1 mRNA and protein expression was observed in both ulcer models, with more pronounced changes in the IMO-WI model.
• Increased Egr-1 levels were associated with decreased Sp1 protein levels, indicating a potential competitive interaction.

Conclusions:

• A competitive interaction between redox-sensitive transcription factors Egr-1 and Sp1 occurs during the early phases of gastric ulcer development.
• This interaction may enhance Egr-1's transcriptional activity by reducing Sp1 activity, contributing to ulcer pathogenesis.