Evidence map›Paper›PMID 42694691›Full record

ArticleFrontiers in immunology2026

Multi-omics analysis identifies fibroblast IGFBP5 as a key target of anti-TNFα therapy in ulcerative colitis.

Peihong Li, Yikun Zhang, Liuqin Zhao, Yiwen Wang, Hongyi Hu, Siqing Guo, Tingting Zhang, Zhancheng Lin, Jiang Lin, Kexin Zeng and 3 more

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In one paragraph

Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

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.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Peihong LiDepartment of Gastroenterology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Yikun ZhangFengxian District Hospital of Traditional Chinese Medicine, Shanghai, China.
Liuqin ZhaoDepartment of Gastroenterology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Yiwen WangDepartment of Internal Medicine, Tianshan Hospital of Traditional Chinese Medicine, Shanghai, China.
Hongyi HuDepartment of Gastroenterology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Siqing GuoDepartment of Coloproctology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Tingting ZhangDepartment of Colorectal Surgery, Shanghai Yangpu Hospital of Traditional Chinese Medicine, Shanghai, China.
Zhancheng LinDepartment of Critical Care Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Jiang LinDepartment of Gastroenterology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Kexin ZengCollege of Plant Protection, Hunan Agricultural University, Changsha, China.
Linda ZhongSchool of Biological Sciences, Nanyang Technological University, Singapore, Singapore.
Changqin LiuDepartment of Gastroenterology, Shanghai Tenth People's Hospital, Shanghai, China.
Boyun SunDepartment of Gastroenterology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Resistance to anti-TNFα therapy (e.g., infliximab) in ulcerative colitis (UC) remains a significant clinical challenge, with the underlying cellular and spatial mechanisms poorly understood. Methods: We integrated bulk transcriptomics, single-cell RNA sequencing (scRNA-seq), and spatial transcriptomics (ST) from clinical cohorts to systematically map the cellular landscape and identify key determinants of treatment response, followed by validation in independent clinical cohorts and Results: Multi-omics cross-analysis pinpointed insulin-like growth factor-binding protein 5 (IGFBP5) as a fibroblast-specific, spatially enriched gene strongly associated with infliximab non-response. Functional analyses linked IGFBP5 to inflammatory pathways and a distinct immune-activated microenvironment. Cell-cell communication analysis revealed that IGFBP5-high fibroblasts exhibit enhanced crosstalk with monocytes, endothelial cells, and T cells via VEGF, MIF, and WNT signaling. Validation in clinical samples and functional experiments confirmed elevated expression of IGFBP5 and its downstream effectors EGR1 and VEGFR2 in non-responders, Mechanistically, IGFBP5 promoted activation of the VEGFR2/EGR1 signaling axis and enhanced the secretion of inflammatory mediators, including IL-6, CXCL12, and CCL2, thereby contributing to a pro-inflammatory fibroblast phenotype. Conclusions: This study establishes fibroblast-derived IGFBP5 as a central mediator of anti-TNFα resistance in UC. The IGFBP5-EGR1-VEGFR2 axis may represent a candidate predictive biomarker and a promising target for overcoming treatment resistance.

Indexed as

Colitis, UlcerativeFibroblastsInsulin-Like Growth Factor Binding Protein 5Tumor Necrosis Factor-alphaGene Expression ProfilingHumansInfliximabMultiomicsSignal TransductionIGFBP5 protein, humanInfliximabInsulin-Like Growth Factor Binding Protein 5Tumor Necrosis Factor-alphaanti-TNFα resistancefibroblastsIGFBP5scRNA-seqspatial transcriptomicsulcerative colitis

Identifiers

PMID42694691
PMCPMC13540427

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