Evidence map›Paper›PMID 42745198›Full record

ArticleNeurogastroenterology and motility2026

Muscularis EGR1 Deficiency Impairs M2 Macrophage Polarization and Disrupts Gastric Motility in Diabetic Gastroparesis.

Ni Xie, Guanhao Su, Ying Wu, Kui Peng, Zhu Mei, Wei Chen, Kai Xu, Baiwen Li

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PubMed Full text at PMC Publisher
In one paragraph

Article in Neurogastroenterology and motility, 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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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Ni XieDepartment of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Guanhao SuDepartment of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.ORCID https://orcid.org/0009-0008-0584-9421
Ying WuDepartment of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Kui PengDepartment of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.ORCID https://orcid.org/0000-0003-1884-7296
Zhu MeiDepartment of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Wei ChenDepartment of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Kai XuDepartment of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Baiwen LiDepartment of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Funding

Clinical Research Innovation Plan of Shanghai General Hospital CTCCR-2021B02National Natural Science Foundation of China 82270568Shanghai Science and Technology Plan Project Foundation 22Y11907800
6 · The paper itself

Abstract

backgroundDiabetic gastroparesis (DGP) is characterized by delayed gastric emptying and limited mechanism-based therapies. Pyloric dysfunction has been associated with loss of interstitial cells of Cajal (ICC) and altered muscularis macrophage polarization. This study examined whether early growth response 1 (EGR1) links macrophage polarization to ICC integrity in DGP.

methodsHuman full-thickness gastric body transcriptomic data (GSE115601) were analyzed using differential expression and exploratory machine learning, with validation in single-cell RNA sequencing data (GSE252126) and clinical pyloric muscularis biopsies. A streptozotocin-induced DGP rat model was used to test local pyloric adeno-associated virus 9 (AAV9)-mediated EGR1 restoration. Macrophage and primary ICC experiments included EGR1 knockdown, thioredoxin 2 (TXN2) rescue, mitochondrial respiration analysis, cytokine profiling, C-C motif chemokine ligand 5 (CCL5) neutralization, and C-C chemokine receptor 5 (CCR5) blockade.

resultsEGR1 was downregulated in DGP gastric body samples and subsequently validated in human pyloric muscularis biopsies, with enrichment in macrophages, particularly M2 macrophages. EGR1 loss reduced TXN2 transcription and mitochondrial oxidative phosphorylation (OXPHOS), impaired M2 polarization, and increased macrophage CCL5 secretion. Conditioned medium from EGR1-deficient macrophages induced Ca

conclusionsMuscularis EGR1 deficiency may promote DGP by disrupting TXN2-dependent macrophage OXPHOS and triggering CCL5/CCR5/NLRP3-mediated ICC injury. Local EGR1 restoration improved gastric motility and may represent a therapeutic strategy.

Indexed as

Diabetes ComplicationsDiabetes Mellitus, ExperimentalEarly Growth Response Protein 1Gastrointestinal MotilityGastroparesisMacrophagesAnimalsHumansInterstitial Cells of CajalMaleRatsEarly Growth Response Protein 1EGR1 protein, humanEgr1 protein, ratdiabetic gastroparesisEGR1interstitial cells of Cajalmacrophages polarizationmitochondrial OXPHOS

Identifiers

PMID42745198
PMCPMC13578571

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