ArticleGut2026
Fibroblast pentose phosphate pathway activation upon decreased circPLCE1 exacerbates intestinal fibrosis in Crohn's disease.
Article in Gut, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
3 citing papers in PubMed.
- Epigenetic modulation of stromal cell states underpins pathological tissue niches in Crohn's disease.Nature immunology · 2026Article
- XYLB promotes malignant behaviors of triple-negative breast cancer via SUSD3 upregulation.Molecular and cellular biochemistry · 2026Article
- Fructose metabolism as an adaptive survival axis in pancreatic cancer: mechanistic insights and therapeutic implications.Frontiers in medicine · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
Abstract
backgroundIntestinal fibrosis, a hallmark complication of Crohn's disease (CD), frequently progresses to stricture formation and surgical intervention. Fibroblast metabolic reprogramming is important in organ fibrosis. However, its role in intestinal fibrogenesis of CD remains elusive.
objectiveWe aim to explore the metabolic reprogramming of fibroblasts and its upstream regulators during intestinal fibrosis of CD.
designWe performed metabolome, single-cell RNA sequencing and spatial transcriptome on paired mucosal and submucosal tissue from the strictured and adjacent non-strictured intestinal segments. The candidate metabolite and metabolic enzymes were verified in primary human intestinal myofibroblasts (HIMFs) and dextran sulfate sodium-induced intestinal fibrotic mice. Next, we identified fibrosis-associated circPLCE1 to regulate the pentose phosphate pathway (PPP) using the circRNA transcriptome. Finally, we studied the functions and mechanisms of circPLCE1 using metabolome, transcriptome, metabolic flux, seahorse assay and RNA pull-down assay in HIMFs and fibroblast-specific circPLCE1 knockdown mice.
resultsMultilayer integrated analysis identified activation of PPP in fibroblasts during intestinal fibrosis of CD. Specifically, xylulokinase (XYLB)-generated xylulose-5-phosphate (Xu5P) promoted extracellular matrix synthesis by epigenetic upregulation of collagen transcription. Moreover, downregulation of circPLCE1 in fibroblasts activated PPP, resulting in increased glycolysis, nicotinamide adenine dinucleotide phosphate production and aggravated intestinal fibrosis in vitro and in vivo. Mechanistically, circPLCE1 directly bound the domain-I of XYLB and competitively inhibited its enzymatic activity. Decreased circPLCE1 restored XYLB activity and accumulation of Xu5P in intestinal fibrosis.
conclusionOur findings delineate a circPLCE1/XYLB/Xu5P axis in fibroblasts which orchestrates PPP and fibrogenesis, unveiling a novel therapeutic target for intestinal fibrosis of CD.
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What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.