Introduction

Helicobacter pylori infection remains a primary driver of chronic gastric inflammation and peptic ulcers worldwide. While clinicians understand the direct impact of the bacteria on epithelial cells, recent research has unveiled a more complex communication network. Specifically, the role of stromal fibroblasts in H. pylori gastritis progression has gained significant attention. These cells, though not directly infected, respond to signals from neighboring epithelial cells to sustain a pro-inflammatory environment.

Mechanisms of H. pylori Gastritis Progression

Consequently, scientists have investigated how signals travel between cell types during infection. They discovered that infected epithelial cells release small vesicles called exosomes. These exosomes carry a specific microRNA known as miR-143-5p. Once these vesicles reach local fibroblasts, they are internalized and the microRNA moves into the nucleus. This internal communication is a critical step in H. pylori gastritis progression, as it transforms healthy fibroblasts into pro-inflammatory mediators.

The Role of NamiRNA-143-5p and ASPN

Notably, miR-143-5p acts as a nuclear activating microRNA (NamiRNA). Instead of silencing genes, it binds to the super-enhancer region of the ASPN gene. Therefore, it increases H3K27ac enrichment and promotes the transcription of Asporin (ASPN). Higher ASPN levels then trigger the secretion of cytokines like IL-4, IL-6, and TGF-β. Furthermore, these cytokines recruit more inflammatory cells to the site, worsening the tissue damage. Studies show that blocking this specific microRNA using antagomirs can significantly reduce inflammation in animal models.

Therapeutic Implications for Gastric Health

This discovery highlights a novel axis in the pathogenesis of gastric diseases. Because the exosomal NamiRNA-143-5p/ASPN pathway drives the inflammatory cycle, it represents a potential therapeutic target. Current treatments focus on bacterial eradication; however, targeting the host's inflammatory response could provide additional relief for patients with refractory gastritis. In the future, specialized miRNA inhibitors might serve as a secondary line of defense against chronic mucosal damage.

Frequently Asked Questions

How does H. pylori communicate with non-infected cells?

The bacteria infect epithelial cells, which then release exosomes containing NamiRNA-143-5p. These exosomes travel to fibroblasts and trigger inflammatory pathways without direct bacterial contact.

What is the role of ASPN in gastric inflammation?

ASPN (Asporin) is a protein that, when upregulated in fibroblasts, stimulates the production of multiple pro-inflammatory cytokines like IL-6 and TGF-β, driving disease progression.

Can targeting NamiRNA-143-5p treat gastritis?

Experimental studies using antagomir-143-5p have successfully reduced cytokine overexpression and gastric inflammation, suggesting it could be a future therapeutic target.

Disclaimer: This content is for informational and educational purposes only. It does not constitute medical advice or replace professional judgment. Refer to the latest local and national guidelines for clinical practice.

References

Zhang Z et al. Epithelial cell-derived exosomes carry NamiRNA-143-5p and promote ASPN expression in fibroblasts to induce Helicobacter pylori infected gastritis progression. Gut Pathog. 2026 Feb 21. doi: 10.1186/s13099-026-00808-6. PMID: 41723544.

Matsushima K et al. The role of gastric fibroblasts in the pathogenesis of H. pylori-induced chronic gastritis. Gastroenterology Research. 2024.

Leung WK et al. MicroRNAs in Helicobacter pylori infection and gastric cancer. Nature Reviews Gastroenterology & Hepatology. 2023.