ArticleGastroenterology2021
WFDC2 Promotes Spasmolytic Polypeptide-Expressing Metaplasia Through the Up-Regulation of IL33 in Response to Injury.
Article in Gastroenterology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 41 citations in OpenAlex.
- Human Epididymis Protein 4 in Cardiovascular Disease: A Fibrosis-Driven Mediator of Tissue Remodeling and Inter-Organ Communication.Circulation reports · 2026Review
- The origins and progression of pyloric metaplasia following gastric mucosal injury.Physiological reviews · 2026Review
- Review
- Amiloride mitigates respiratory distress caused by WFDC2 deficiency via inhibiting the epithelial sodium channel.Nature communications · 2026Article
- Gastric intestinal metaplasia: unraveling the multifactorial pathogenesis and advancing risk stratification for gastric cancer prevention.Cellular and molecular life sciences : CMLS · 2026Review
- Refined Jianpi Huayu Jiedu Decoction Attenuates TAM-Induced Spasmolytic Polypeptide-Expressing Metaplasia (SPEM) by Modulating LCN2-Associated Mitochondrial Dysfunction.Pharmaceuticals (Basel, Switzerland) · 2026Article
- A single-cell multi-omics atlas defines the cellular and molecular landscape of gastric intestinal metaplasia.Journal of translational medicine · 2026Article
- Pristimerin ameliorates spasmolytic polypeptide-expressing metaplasia by modulatingWorld journal of gastroenterology · 2026Article
- Roles of interleukins in spasmolytic polypeptide‑expressing metaplasia (Review).International journal of oncology · 2026Review
- Revolutionizing Gastric Cancer Prevention: Novel Insights on Gastric Mucosal Inflammation-Cancer Transformation and Chinese Medicine.Chinese journal of integrative medicine · 2025Review
- Cathartocytosis: Jettisoning of cellular material during reprogramming of differentiated cells.Cell reports · 2025Article
- Article
- H. Pylori-Facilitated TERT/Wnt/β-Catenin Triggers Spasmolytic Polypeptide-Expressing Metaplasia and Oxyntic Atrophy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Luteolin improves precancerous conditions of the gastric mucosa by binding STAT3 and inhibiting LCN2 expression.International journal of biological sciences · 2025Article
- Precancerous pathways to gastric cancer: a review of experimental animal models recapitulating the correa cascade.Frontiers in cell and developmental biology · 2025Review
- Single-Cell Sequencing Reveals PD-L1-Mediated Immune Escape Signaling in Lung Adenocarcinoma.Journal of Cancer · 2025Article
- Advances in modeling gastric intestinal metaplasia: a comprehensive review of experimental models and mechanistic insights.Frontiers in oncology · 2025Review
- Emerging role of spasmolytic polypeptide-expressing metaplasia in gastric cancer.Journal of gastrointestinal oncology · 2024Review
- The Importance of Th2 Immune Responses in Mediating the Progression of Gastritis-Associated Metaplasia to Gastric Cancer.Cancers · 2024Review
- Tumour-associated macrophages in gastric cancer: From function and mechanism to application.Clinical and translational medicine · 2023Review
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsWAP 4-disulfide core domain protein 2 (WFDC2), also known as human epididymis protein 4, is a small secretory protein that is highly expressed in fibrosis and human cancers, particularly in the ovaries, lungs, and stomach. However, the role of WFDC2 in carcinogenesis is not fully understood. The present study aimed to investigate the role of WFDC2 in gastric carcinogenesis with the use of preneoplastic metaplasia models.
methodsThree spasmolytic polypeptide-expressing metaplasia (SPEM) models were established in both wild-type and Wfdc2-knockout mice with DMP-777, L635, and high-dose tamoxifen, respectively. To reveal the functional role of WFDC2, we performed transcriptomic analysis with DMP-777-treated gastric corpus specimens.
resultsWfdc2-knockout mice exhibited remarkable resistance against oxyntic atrophy, SPEM emergence, and accumulation of M2-type macrophages in all 3 SPEM models. Transcriptomic analysis revealed that Wfdc2-knockout prevented the up-regulation of interleukin-33 (IL33) expression in the injured mucosal region of SPEM models. Notably, supplementation of recombinant WFDC2 induced IL33 production and M2 macrophage polarization, and ultimately promoted SPEM development. Moreover, long-term treatment with recombinant WFDC2 was able to induce SPEM development.
conclusionsWFDC2 expressed in response to gastric injury promotes SPEM through the up-regulation of IL33 expression. These findings provide novel insights into the role of WFDC2 in gastric carcinogenesis.
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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.