ArticleThe Journal of clinical investigation2022
R-spondin/YAP axis promotes gastric oxyntic gland regeneration and Helicobacter pylori-associated metaplasia in mice.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Dynamic role of gastric stem cells and chief cells in precancerous lesions of gastric cancer: global knowledge mapping and emerging trends based on bibliometric analysis from 2004 to 2024.Frontiers in oncology · 2025Pooled it
- Helicobacter pylori triggers gastric mucosal remodeling toward a fetal-like transcriptional program via stromal IL-1β signaling.Nature communications · 2026Article
- Building and regenerating intestines by manipulating intestinal stem cells.Nature reviews. Gastroenterology & hepatology · 2026Review
- Mesenchymal R-spondin 3 promotes an immunogenic tumor microenvironment with adaptive immune resistance in human gastric adenocarcinoma.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2026Article
- Wnt regulates cellular differentiation and retinoid metabolism genes in the mouse stomach.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- The LGR5/TFF2 ratio as a stem cell biomarker predicts high-risk status in chronic atrophic gastritis: a retrospective cohort study.BMC gastroenterology · 2026Article
- Regulation of STK38 by autophagy governs YAP1 activity during paligenosis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Recent advances in spasmolytic polypeptide expressing metaplasia research.World journal of gastrointestinal oncology · 2026Review
- Decoding mechanosensitive genes in cardiac fibroblasts via 3D hydrogel models of fibrosis.Scientific reports · 2025Article
- Helicobacter pylori, microbiota and gastric cancer - principles of microorganism-driven carcinogenesis.Nature reviews. Gastroenterology & hepatology · 2025Review
- Deciphering of intra-tumoural heterogeneity and the interplay between metastasis-associated meta-program and myofibroblasts in gastric cancer.Clinical and translational medicine · 2025Article
- H. Pylori-Facilitated TERT/Wnt/β-Catenin Triggers Spasmolytic Polypeptide-Expressing Metaplasia and Oxyntic Atrophy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Regulation of RSPO3-LGR4 Signaling: Emerging Role in Inflammation Revealed by Network Analysis.Archives of clinical and biomedical research · 2025Article
- Gastric Organoid, a Promising Modeling for Gastric Stem Cell Homeostasis and Therapeutic Application.International journal of stem cells · 2024Review
- [Role of R-spondin 2 on osteogenic differentiation of bone marrow mesenchymal stem cells and bone metabolism in ovariectomized mice].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2024Article
- Gastric intestinal metaplasia: progress and remaining challenges.Journal of gastroenterology · 2024Review
- The porcine islet-derived organoid showed the characteristics as pancreatic duct.Scientific reports · 2024Article
- Region-specific Wnt signaling responses promote gastric polyp formation in patients with familial adenomatous polyposis.JCI insight · 2023Article
- Differential sensitivity to Wnt signaling gradients in human gastric organoids derived from corpus and antrum.American journal of physiology. Gastrointestinal and liver physiology · 2023Article
- The Hippo signaling pathway in gastric cancer.Acta biochimica et biophysica Sinica · 2023Review
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11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The stomach corpus epithelium is organized into anatomical units that consist of glands and pits. Mechanisms that control the cellular organization of corpus glands and enable their recovery upon injury are not well understood. R-spondin 3 (RSPO3) is a WNT-signaling enhancer that regulates stem cell behavior in different organs. Here, we investigated the function of RSPO3 in the corpus during homeostasis, upon chief and/or parietal cell loss, and during chronic Helicobacter pylori infection. Using organoid culture and conditional mouse models, we demonstrate that RSPO3 is a critical driver of secretory cell differentiation in the corpus gland toward parietal and chief cells, while its absence promoted pit cell differentiation. Acute loss of chief and parietal cells induced by high dose tamoxifen - or merely the depletion of LGR5+ chief cells - caused an upregulation of RSPO3 expression, which was required for the initiation of a coordinated regenerative response via the activation of yes-associated protein (YAP) signaling. This response enabled a rapid recovery of the injured secretory gland cells. However, in the context of chronic H. pylori infection, the R-spondin-driven regeneration was maintained long term, promoting severe glandular hyperproliferation and the development of premalignant metaplasia.
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