Helicobacter pylori Activates Matrix Metalloproteinase 10 in Gastric Epithelial Cells via EGFR and ERK-mediated Pathways

Angela Costa; Rui Ferreira; Ines Pinto-Ribeiro; Ioanna Sougleri; Maria Oliveira; Laura Carreto; Manuel Santos; Dionyssios Sgouras; Fatima Carneiro; Marina Leite; Ceu Figueiredo

Helicobacter pylori Activates Matrix Metalloproteinase 10 in Gastric Epithelial Cells via EGFR and ERK-mediated Pathways

Angela Costa ^{1, 2} Rui Ferreira ^{1, 2} Ines Pinto-Ribeiro ^{1, 2} Ioanna Sougleri ³ Maria Oliveira ^{4, 1, 5} Laura Carreto ⁶ Manuel Santos ⁶ Dionyssios Sgouras ³ Fatima Carneiro ^{1, 2, 5, 7} Marina Leite ^{1, 2} Ceu Figueiredo ^{1, 2, 5, *}

* Corresponding author

1 I3S - Instituto de Investigação e Inovação em Saúde

2 IPATIMUP - Instituto de Patologia e Imunologia Molecular da Universidade do Porto

3 Laboratoire de microbiologie médicale [Athènes]

4 INEB - Instituto de Engenharia Biomédica

5 FMUP - Faculdade de Medicina da Universidade do Porto [Porto]

6 Universidade de Aveiro

7 Hospital de São João [Porto]

Abstract : Helicobacter pylori colonizes the human stomach and increases the risk for peptic ulcer disease and gastric carcinoma. H. pylori upregulates the expression and activity of several matrix metalloproteinases (MMPs) in cell lines and in the gastric mucosa. The aim of this study was to explore the mechanisms leading to upregulation of MMP10 in gastric epithelial cells induced by H. pylori. Infection of gastric cells with H. pylori led to an increase in levels of MMP-10 messenger RNA, protein secretion, and activity. cagA knockout mutants or CagA phosphorylation-defective mutants failed to increase MMP10 expression. These results were confirmed in infection experiments with clinical isolates with known cagA status and in human gastric biopsy specimens. Treatment of cells with chemical inhibitors of the receptor tyrosine kinase EGFR and the kinase Src abrogated H. pylori-induced MMP10 expression. Inhibitors of ERK1/2 and JNK kinases abolished and significantly decreased H. pylori-induced MMP10 expression, respectively, whereas inhibition of the kinase p38 had no effect. Finally, inhibition of MMP10 expression by small interfering RNA led to a decrease in the gastric cell-invasive phenotype mediated by the infection. In conclusion, CagA-positive H. pylori strains stimulate MMP10 expression. MMP-10 modulation occurs via EGFR activation in a process that involves Src, ERK, and JNK pathways. MMP-10 may be implicated in H. pylori-mediated extracellular matrix remodeling.

Keywords : CagA Helicobacter pylori MMP-10 EGFR invasion

Document type :

Journal articles

Domain :

Life Sciences [q-bio] / Microbiology and Parasitology / Bacteriology

Life Sciences [q-bio] / Human health and pathology / Hépatology and Gastroenterology

Complete list of metadatas

https://hal-riip.archives-ouvertes.fr/pasteur-02195913
Contributor : Dionyssios Sgouras <>
Submitted on : Friday, July 26, 2019 - 3:48:16 PM
Last modification on : Wednesday, July 31, 2019 - 1:12:24 AM

Helicobacter pylori Activates Matrix Metalloproteinase 10 in Gastric Epithelial Cells via EGFR and ERK-mediated Pathways

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Helicobacter pylori Activates Matrix Metalloproteinase 10 in Gastric Epithelial Cells via EGFR and ERK-mediated Pathways

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