REGγ Links Inflammation to Fibrosis in Post-Necrotizing Enterocolitis Intestinal Strictures by Activating...

Area of Science:

• Gastroenterology
• Molecular Biology
• Pathology

Background:

• Intestinal stricture is a common complication of necrotizing enterocolitis (NEC), leading to significant morbidity.
• Fibrosis driven by inflammation is the primary cause of stricture development, but underlying molecular pathways are not fully understood.
• Regenerating Gamma (REGγ) has been previously linked to inflammation severity in NEC.

Purpose of the Study:

• To investigate the role of REGγ in the development of fibrosis in post-NEC intestinal strictures.
• To elucidate the molecular mechanisms by which REGγ contributes to inflammation-fibrosis crosstalk.

Main Methods:

• Analysis of human NEC stricture specimens.
• Single-cell RNA sequencing and immunofluorescence.
• In vitro studies using fibroblast cell cultures stimulated with TGF-β1 or TNF-α.
• Murine models of intestinal fibrosis.

Main Results:

• Elevated REGγ levels in human strictures correlated with fibrotic severity.
• REGγ was enriched in fibroblasts within the strictures.
• REGγ silencing inhibited fibroblast activation, proliferation, and migration.
• TNF-α-induced REGγ expression was mediated by NF-κB signaling.
• REGγ deficiency reduced inflammation and fibrosis in murine models.

Conclusions:

• REGγ is a critical mediator of inflammation-fibrosis crosstalk in post-NEC intestinal strictures.
• Targeting REGγ presents a potential therapeutic strategy for mitigating NEC-associated intestinal strictures.