Omics · study · 2026
Mesenteric inflammation-associated fibroblasts promote intestinal epithelial dysfunction and Crohn’s disease progression
Listed in NCBI GEO
The mesentery contributes to Crohn’s disease (CD) progression, promoting immune cell infiltration and fibrosis.
Description
Mesenteric fibroblasts, activated by pro-fibrotic cytokines such as TGF-β, stimulate fibrosis through excessive extracellular matrix (ECM) deposition, leading to intestinal thickening and stricture formation. In this study, we aim to explore the specific role of the mesenteric inflammation-associated fibroblasts in the development of CD.
Mesenteric inflammation-associated fibroblasts (IAFs) and normal fibroblasts (NFs) were isolated from the mesenteries of patients with Crohn’s disease (CD) and individuals with non-cancerous colonic polyps (control samples) using magnetic-activated cell sorting. Phenotypic differences between the fibroblast populations were analyzed using cell viability, invasion, and collagen contraction assays. Co-culture systems, including transwell and 3D Matrigel co-cultures, were employed to evaluate the effects of NFs and IAFs on the behavior of colonic epithelial cancer cell lines (Caco-2 and HT-29).
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RNA-seq followed by gene set enrichment and gene ontology analyses identified IAF-specific genes associated with CD progression. Candidate genes were further validated by immunofluorescence staining in mesenteric tissues from CD patients. IAFs exhibited higher cell growth, wound healing, invasion, and collagen contraction activities compared with NFs.
In a 3D Matrigel co-culture system, IAFs induced abnormal lumen formation and invasive structures in Caco-2 spheres. Consistently, IAFs promoted epithelial barrier disruption in a fluorescein transport assay using a transwell co-culture system. Conditioned media from IAFs upregulated mesenchymal markers in Caco-2 cells.
Furthermore, transcriptomic analyses revealed enrichment of ECM organization chemokine- and cytokine-mediated signaling pathways in IAFs. These findings indicate that mesenteric IAFs actively contribute to epithelial barrier dysfunction and disease progression in CD. Targeting IAF-derived chemokines may represent a novel therapeutic strategy.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE315nnn/GSE315214 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE315214 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1395134 ncbi.nlm.nih.gov/bioproject/PRJNA1395134 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Cancer 75% · Disease 75% · RNA sequencing 65%
Provenance · 1 source records, 10 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE315214 | 13 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:cancer | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[disease].local:disease:disease | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |