ArticleCellular and molecular gastroenterology and hepatology2022
Elevated Protein Kinase A Activity in Stomach Mesenchyme Disrupts Mesenchymal-epithelial Crosstalk and Induces Preneoplasia.
Article in Cellular and molecular gastroenterology and hepatology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.
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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.
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.
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Who cites it
5 citing papers in PubMed, 1 synthesis or guideline pooled it, 5 citations in OpenAlex.
- Global research trends in signaling pathways of spasmolytic polypeptide-expressing metaplasia pathogenesis: a bibliometric analysis.Frontiers in oncology · 2025Pooled it
- GDF9, NPHS1, and RET Mark Gastric Neuroendocrine Cells and Their Disruption in a PKA-Driven Gastric Preneoplasia Model.International journal of molecular sciences · 2026Article
- Alternative splicing of CARM1 regulated by LincGET-guided paraspeckles biases the first cell fate in mammalian early embryos.Nature structural & molecular biology · 2024Article
- Gastric intestinal metaplasia: progress and remaining challenges.Journal of gastroenterology · 2024Review
- Stroma New Tune: Emerging Role of PKA in Maintaining Gastric Homeostasis.Cellular and molecular gastroenterology and hepatology · 2022Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsMesenchymal-epithelial crosstalk (MEC) in the stomach is executed by pathways such as bone morphogenetic protein (BMP) and extracellular signal-regulated kinase (ERK). Mis-regulation of MEC disrupts gastric homeostasis and causes tumorigenesis. Protein Kinase A (PKA) crosstalks with BMP and ERK signaling; however, PKA function(s) in stomach development and homeostasis remains undefined.
methodsWe generated a novel Six2-Cre
resultsLineage tracing showed that Six2-Cre activity in the stomach is restricted to the mesenchymal compartment. CA-PKA mice showed disruption of gastric homeostasis characterized by aberrant mucosal development and epithelial hyperproliferation; ultimately developing multiple features of gastric corpus preneoplasia including decreased parietal cells, mucous cell hyperplasia, spasmolytic peptide expressing metaplasia with intestinal characteristics, and dysplastic and invasive cystic glands. Furthermore, mutant corpus showed marked chronic inflammation characterized by infiltration of lymphocytes and myeloid-derived suppressor cells along with the upregulation of innate and adaptive immune system components. Striking upregulation of inflammatory mediators and STAT3 activation was observed. Mechanistically, we determined there is an activation of ERK1/2 and downregulation of BMP/SMAD signaling characterized by marked upregulation of BMP inhibitor gremlin 1.
conclusionsWe report a novel role of PKA signaling in gastric MEC execution and show that PKA activation in the gastric mesenchyme drives preneoplasia by creating a proinflammatory and proproliferative microenvironment associated with the downregulation of BMP/SMAD signaling and activation of ERK1/2.
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Registered trials
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.