Evidence map›Paper›PMID 38750695›Full record

ArticleJournal of advanced research2025

Mesenteric adipose-derived exosomal TINAGL1 enhances intestinal fibrosis in Crohn's Disease via SMAD4.

Yidong Chen, Junrong Li, Xiaopeng Zhang, Shuang Li, Yiyu Cheng, Xiaoyu Fu, Jiamin Li, Liangru Zhu

Abstract read
In one paragraph

Article in Journal of advanced research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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

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.

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

13 citing papers in PubMed, 1 synthesis or guideline pooled it.

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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

8 authors.

Yidong ChenDivision of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Junrong LiDivision of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Xiaopeng ZhangDivision of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Shuang LiDivision of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Yiyu ChengDivision of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Xiaoyu FuDivision of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Jiamin LiDivision of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Liangru ZhuDivision of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: zhuliangru@hust.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionCrohn's Disease (CD) is a chronic inflammatory condition characterized by intestinal fibrosis, severely impacting patient quality of life. The molecular mechanisms driving this fibrosis remain inadequately understood. Recent evidence implicates mesenteric adipose tissue (MAT) in CD pathogenesis, particularly through its exosome secretion, which may influence fibrogenic pathways. Understanding the role of MAT-derived exosomes is crucial for unraveling these molecular processes.

objectivesThis study aims to elucidate the role of MAT-derived exosomes in CD-related intestinal fibrosis. We focus on investigating their molecular composition and the potential impact on fibrosis progression, with an emphasis on identifying novel therapeutic targets.

methodsWe induced chronic intestinal inflammation in mice using dinitrobenzene sulfonic acid (DNBS), simulating CD-like fibrosis. Exosomes were isolated from DNBS-treated mice (MG) and normal controls (NG) for characterization using electron microscopy and proteomic analysis. Additionally, human colonic fibroblasts were exposed to exosomes from CD patients and healthy individuals, with subsequent assessment of fibrogenesis through proteomic and RNA sequencing analyses.

resultsProteomic analyses revealed a significant activation of the TGF-β signaling pathway in MG-treated mice compared to controls, correlating with enhanced intestinal fibrosis. In vitro experiments demonstrated that colonic fibroblasts exposed to CD patient-derived exosomes exhibited increased fibrogenic activity. Protein docking and co-immunoprecipitation studies suggested a critical interaction between TINAGL1 and SMAD4, enhancing fibrosis. Importantly, in vivo experiments corroborated that recombinant TINAGL1 protein exacerbated DNBS-induced intestinal fibrosis.

conclusionOur findings highlight the pivotal role of MAT-derived exosomes, particularly those carrying TINAGL1, in the progression of intestinal fibrosis in CD. The involvement of the TGF-β signaling pathway, especially the SMAD4 protein, offers new insights into the molecular mechanisms of CD-related fibrosis and presents potential targets for therapeutic intervention.

Indexed as

Adipose TissueCrohn DiseaseExosomesMesenteryRNA, Long NoncodingSmad4 ProteinAnimalsDisease Models, AnimalFemaleFibroblastsFibrosisHumansIntestinesMaleMiceMice, Inbred C57BLRNA, Long NoncodingSmad4 ProteinSMAD4 protein, humanTransforming Growth Factor betaCrohn's DiseaseExosomesIntestinal FibrosisTGF-β/SMAD4 SignalingTINAGL1

Identifiers

PMID38750695
PMCPMC11976418

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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 OpenQuestion graph.