Garlic-Derived Exosomes Alleviate Intestinal Fibrosis in Crohn's Disease by Modulating PFKFB3-Mediated Metabolic...

Area of Science:

• Gastroenterology
• Cell Biology
• Biochemistry

Background:

• Crohn's disease (CD) is a chronic inflammatory bowel disease often complicated by intestinal fibrosis.
• Current therapies are ineffective against fibrotic progression, necessitating novel treatment approaches.

Purpose of the Study:

• To investigate the anti-fibrotic effects of garlic-derived exosomes (GDE) in a model of intestinal fibrosis.
• To elucidate the underlying mechanism involving fibroblast metabolic reprogramming and PFKFB3.

Main Methods:

• In vitro studies using TGF-β1-treated intestinal fibroblasts.
• In vivo studies using a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced mouse model of colitis.
• Analysis of fibrosis markers (hydroxyproline, COL1A2, COL3A1, α-SMA) and PFKFB3 expression.
• Gene interruption and pharmacological inhibition of PFKFB3.

Main Results:

• GDE reduced fibrosis markers and inhibited fibrosis-related protein expression in fibroblasts and mouse colon tissue.
• GDE attenuated phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 3 (PFKFB3) expression.
• PFKFB3 inhibition blocked GDE's anti-fibrotic effects by altering glycolysis and metabolic reprogramming.
• Fibroblast-specific Pfkfb3 deficiency reduced colon fibrosis in TNBS-induced mice.

Conclusions:

• GDE exerts anti-fibrotic effects by inhibiting fibroblast metabolic reprogramming through PFKFB3 regulation.
• This study identifies PFKFB3 as a potential therapeutic target for intestinal fibrosis in CD.
• GDE represents a promising novel therapeutic strategy for treating CD-associated intestinal fibrosis.