Helicobacter pylori promotes gastric fibroblast proliferation and migration by expulsing exosomal miR-124-3p

Jun Li; Xiangji Li; Zheng Zhang; Shidong Wang; Xinyuan Huang; Li Min; Peng Li

doi:10.1016/j.micinf.2023.105236

Helicobacter pylori promotes gastric fibroblast proliferation and migration by expulsing exosomal miR-124-3p

Microbes Infect. 2024 Jan-Feb;26(1-2):105236. doi: 10.1016/j.micinf.2023.105236. Epub 2023 Oct 7.

Authors

Jun Li¹, Xiangji Li², Zheng Zhang², Shidong Wang², Xinyuan Huang², Li Min³, Peng Li⁴

Affiliations

¹ Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, 100050 Beijing, PR China; Department of Gastroenterology, Chui Yang Liu Hospital Affiliated to Tsinghua University, 100020 Beijing, PR China.
² Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, 100050 Beijing, PR China.
³ Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, 100050 Beijing, PR China. Electronic address: minli@ccmu.edu.cn.
⁴ Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, 100050 Beijing, PR China. Electronic address: lipeng@ccmu.edu.cn.

PMID: 37813158
DOI: 10.1016/j.micinf.2023.105236

Abstract

Gastric fibroblasts (GFs) are direct targets of Helicobacter pylori (H. pylori). GFs infected with H. pylori exhibit marked changes in their morphology and biological behavior. However, the molecular mechanisms by which H. pylori regulates GFs remain unknown. In this study, we cocultured GFs with H. pylori for 48 h. As a result, GFs exhibited an elongated and spindle-shaped morphology. Further, cancer-associated fibroblast (CAF) biomarkers were increased, and related behaviors were significantly enhanced in H. pylori-activated GFs. The number of extracellular vesicles (EVs) secreted by H. pylori-activated GFs remarkably increased. The miR-124-3p level was increased in secreted EVs but decreased in the cytoplasm of H. pylori-activated GFs. Overexpression of miRNA-124-3p in the original GFs significantly suppressed their proliferation and migration. In addition, the migration-promoting effects of H. pylori-activated GFs were suppressed by miR-124-3p and GW4869, which blocked EV generation. Finally, pull-down and luciferase assays revealed that SNAI2 is a target of miR-124-3p. The migration-inhibitory effects of GFs treated with miR-124-3p were eliminated by the overexpression of SNAI2, and the upregulation of SNAI2 in H. pylori-activated GFs was partially alleviated by miR-124-3p or GW4869. Overall, H. pylori infection promotes the proliferation and migration of GFs by accelerating the expulsion of EVs carrying miRNA-124-3p, a SNAI2 inhibitor.

Keywords: Extracellular vesicles; Gastric fibroblast; Helicobacter pylori; SNAI2; miRNA-124-3p.

MeSH terms

Aniline Compounds*
Benzylidene Compounds*
Cell Line, Tumor
Cell Proliferation
Helicobacter pylori*
Humans
MicroRNAs* / genetics
Stomach Neoplasms*

Substances

GW 4869
MicroRNAs
MIRN124 microRNA, human
Aniline Compounds
Benzylidene Compounds