Amprenavir Mitigates Pepsin-Induced Transcriptomic Changes in Normal and Precancerous Esophageal Cells

Area of Science:

• Gastroenterology and Molecular Biology
• Investigating cellular responses to reflux components
• Exploring therapeutic targets for esophageal diseases

Background:

• Gastroesophageal reflux disease (GERD) is linked to esophageal inflammation and cancer.
• Esophageal adenocarcinoma (EAC) incidence rises despite proton pump inhibitor (PPI) use.
• Non-acidic reflux components like pepsin may drive GERD progression.

Purpose of the Study:

• To analyze pepsin-induced transcriptomic changes in esophageal cells.
• To evaluate the protective effect of amprenavir against pepsin injury.
• To compare cellular responses in normal (Het-1A) and Barrett's (BAR-T) cells.

Main Methods:

• Transcriptomic profiling (RNA-seq) of esophageal cells (Het-1A, BAR-T) treated with pepsin and/or amprenavir.
• Pathway analysis using Ingenuity Pathway Analysis.
• Differential gene expression analysis with FDR ≤ 0.05 and |log₂FC| ≥ 0.375.

Main Results:

• Pepsin altered mitochondrial function, oxidative phosphorylation, and inflammatory pathways.
• Amprenavir mitigated pepsin-induced transcriptomic changes, preserving mitochondrial and stress pathways.
• Barrett's cells showed enhanced wound-healing responses, while normal cells displayed more stress pathway alterations.

Conclusions:

• Pepsin induces transcriptomic dysregulation in esophageal cells under non-acidic conditions.
• Amprenavir demonstrates potential in counteracting peptic injury.
• Further research is warranted to explore amprenavir's role in GERD and EAC prevention.