Epithelial Hypusination Regulates Helicobacter pylori-induced Gastric Inflammation

Area of Science:

• Molecular Biology
• Gastroenterology
• Immunology

Background:

• Hypusine is a unique amino acid modification of eukaryotic initiation factor 5A (EIF5A).
• Hypusination of EIF5A is catalyzed by deoxyhypusine synthase (DHPS) and is crucial for translation.
• The role of epithelial hypusination in gastric inflammation, particularly in response to Helicobacter pylori, remains unclear.

Purpose of the Study:

• To investigate the contribution of the epithelial hypusination pathway to gastric inflammation induced by H. pylori.
• To explore the potential of targeting DHPS-dependent EIF5A hypusination as a therapeutic strategy.

Main Methods:

• Immunohistochemical analysis of DHPS and hypusinated EIF5A (EIF5A^Hyp) in human gastric biopsies.
• Generation of a mouse model with epithelial-specific deletion of Dhps (Dhps^Δepi).
• Quantitative proteomics of isolated gastric epithelial cells (GECs) from naive and infected mice.

Main Results:

• Increased DHPS and EIF5A^Hyp expression in the gastric mucosa of H. pylori-infected patients, particularly in GECs and immune cells.
• Dhps^Δepi mice showed attenuated gastric inflammation upon H. pylori infection, without affecting bacterial load.
• Proteomic analysis revealed that Dhps deletion altered protein expression related to injury and disease, and upon infection, reduced inflammatory responses in GECs.

Conclusions:

• Epithelial hypusination supports H. pylori-driven gastric inflammation by modulating inflammatory and immune responses in GECs.
• DHPS-dependent EIF5A hypusination does not influence bacterial persistence.
• Targeting DHPS could be a novel therapeutic strategy for H. pylori-associated gastric mucosal injury and disease progression.