Fibroblast pentose phosphate pathway activation upon decreased circPLCE1 exacerbates intestinal fibrosis in Crohn’s disease
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By
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May 1, 2026
Objective:
To investigate the role of the pentose phosphate pathway (PPP) and circPLCE1 in fibroblast metabolism and intestinal fibrosis in Crohn's disease, highlighting the significance of circPLCE1.
Key Findings:
- Activation of the pentose phosphate pathway (PPP) in fibroblasts is linked to intestinal fibrosis in Crohn's disease.
- Xylulokinase (XYLB) generates xylulose-5-phosphate (Xu5P), promoting collagen transcription in fibrotic fibroblasts.
- Downregulation of circPLCE1 in fibroblasts drives PPP activation by enhancing XYLB activity, leading to increased Xu5P levels.
Interpretation:
The study identifies a circPLCE1/XYLB/Xu5P regulatory axis that connects circRNA biology to fibroblast metabolism, suggesting potential therapeutic targets for intestinal fibrosis and emphasizing the need for further exploration.
Limitations:
- The study primarily focuses on human intestinal tissues, which may limit generalizability to other forms of fibrosis.
- Further research is needed to explore the therapeutic implications of targeting the circPLCE1/XYLB/Xu5P axis, considering potential confounding factors.
Conclusion:
This research highlights the metabolic reprogramming in fibroblasts during intestinal fibrosis and suggests that targeting the circPLCE1/XYLB/Xu5P axis could offer new therapeutic strategies specifically for Crohn's disease-related fibrosis.
