Early and late genome-wide gastric epithelial transcriptome response during infection with the human carcinogen Helicobacter pylori

• Published in: Cell insight Vol. 1; no. 3; p. 100032
• Main Authors: Sharafutdinov, Irshad, Ekici, Arif, Vieth, Michael, Backert, Steffen, Linz, Bodo
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier 01-06-2022
• Subjects: Apoptosis; Cancer; Helicobacter; HtrA; Inflammation; RNA-seq; HtrA; Inflammation; RNA-seq; Helicobacter; Apoptosis; Cancer
• ISSN: 2772-8927; 2772-8927
• DOI: 10.1016/j.cellin.2022.100032

Infection of the stomach by
is a major risk factor for the development of gastric cancer. Colonization of the gastric epithelium leads to the activation of multiple disease-related signaling pathways. Serine protease HtrA represents an important secreted virulence factor that mediates cleavage of cellular junctions. However, its potential role in nuclear responses is unknown. Here, we performed a genome-wide RNA-seq analysis of polarized gastric epithelial cells infected by wild-type (wt) and Δ
mutant bacteria. Fluorescence microscopy showed that
wt, but not Δ
bacteria, preferably localized at cellular junctions. Our results pinpointed early (2 h) and late (6 h) transcriptional responses, with most differentially expressed genes at 6 h post infection. The transcriptomes revealed HtrA-dependent targeting of genes associated with inflammation and apoptosis (e.g.
,
,
). Accordingly, infection with the Δ
mutant induced increased apoptosis rates in host cells, which was associated with reduced
CagA expression. In contrast, transcription of various carcinogenesis-associated genes (e.g.
,
) was affected by
independent of HtrA. These findings suggest that
disturbs previously unknown molecular pathways in an HtrA-dependent and HtrA-independent manner, and provide valuable new insights of this significant pathogen in humans and thus potential targets for better controlling the risk of malignant transformation.