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Deoxycholic acid-stimulated macrophage-derived exosomes promote spasmolytic polypeptide-expressing metaplasia in the

Xianjun Xu1, Jinnian Cheng2, Shengzheng Luo1

  • 1Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Biochemical and Biophysical Research Communications
|February 9, 2020
PubMed
Abstract

Insights

Deoxycholic acid promotes spasmolytic polypeptide-expressing metaplasia (SPEM) through macrophage-derived exosomes. This study reveals a novel mechanism linking bile acids, inflammation, and gastric cancer risk factors.

Area of Science:

  • Gastroenterology
  • Oncology
  • Cell Biology

Background:

  • Spasmolytic polypeptide-expressing metaplasia (SPEM) is a key risk factor for gastric cancer.
  • Chronic inflammation, involving macrophages and bile acids, is implicated in SPEM and intestinal metaplasia.
  • The specific role of bile acids and macrophage-derived exosomes in SPEM development remains unclear.

Purpose of the Study:

  • To investigate the role of deoxycholic acid-stimulated macrophage-derived exosomes in the development of SPEM.
  • To elucidate the underlying mechanisms by which bile acids may influence SPEM.

Main Methods:

  • Mice were administered deoxycholic acid intragastrically to induce SPEM in vivo.
  • Macrophage-derived exosomes were isolated from deoxycholic acid-stimulated macrophages in vitro.
  • Gastric organoids were co-cultured with these exosomes, and SPEM markers were analyzed using immunofluorescence and qPCR.

Main Results:

  • Deoxycholic acid administration increased macrophage and SPEM markers in mouse gastric tissues.
  • Macrophage-derived exosomes were internalized by gastric organoids.
  • Exosomes from deoxycholic acid-stimulated macrophages significantly increased SPEM marker expression in gastric organoids.

Conclusions:

  • Macrophage-derived exosomes represent a novel mechanism by which deoxycholic acid contributes to SPEM.
  • This finding offers potential new therapeutic targets for preventing gastric cancer progression.
Keywords:
Deoxycholic acidExosomesGastric organoidsMacrophagesSpasmolytic polypeptide-expressing metaplasia

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