Infection with a hypervirulent strain of Helicobacter pylori primes gastric cells toward intestinal transdifferentiation. (January 2022)

• Record Type: Journal Article
• Authors: Saberi, Samaneh; Esmaeili, Maryam; Tashakoripour, Mohammad; Eshagh Hosseini, Mahmoud; Baharvand, Hossein; Mohammadi, Marjan
• Is Part Of: Microbial pathogenesis. Volume 162(2022)
• Publication Date: 2022-01
• Subjects: Helicobacter pylori -- Wnt signalling -- Intestinal metaplasia -- Gastric cancer -- Transdifferentiation; Pathogenic microorganisms -- Periodicals; Pathology, Molecular -- Periodicals; Communicable Diseases -- microbiology -- Periodicals; Communicable Diseases -- parasitology -- Periodicals; Micro-organismes pathogènes -- Périodiques; Pathologie moléculaire -- Périodiques; Electronic journals; 616.9041
• DOI: 10.1016/j.micpath.2021.105353
• Languages: English
• ISSNs: 0882-4010

Abstract

Abstract: Background: Intestinal metaplasia, gastric-to-intestinal transdifferentiation, occurs as a result of the misexpression of certain regulatory factors, leading to genetic reprogramming. Here, we have evaluated the H. pylori -induced expression patterns of these candidate genes. Methods: The expression levels of 1) tissue-specific transcription factors ( RUNX3, KLF5, SOX2, SALL4, CDX1 and CDX 2), 2) stemness factors ( TNFRSF19, LGR5, VIL1 ) and 3) tissue-specific mucins ( MUC5AC, MUC2 ) were evaluated by quantitative real-time PCR in gastric primary cells (GPCs), in parallel with two gastric cancer (MKN45 and AGS) cell lines, up to 96h following H. pylori infection. Results: Following H. pylori infection of GPCs, RUNX3 declined at 24h post infection (−6.2 ± 0.3) and remained downregulated for up to 96h. Subsequently, overexpression of self-renewal and pluripotency transcription factors, KLF5 (3.6 ± 0.2), SOX2 (7.6 ± 0.5) and SALL4 (4.3 ± 0.2) occurred. The expression of TNFRSF19 and LGR5, demonstrated opposing trends, with an early rise of the former (4.5 ± 0.3) at 8h, and a simultaneous fall of the latter ( - 1.8 ± 0.5). This trend was reversed at 96h, with the decline in TNFRSF19 (−5.5 ± 0.2), and escalation of LGR5 (2.6 ± 0.2) and VIL1 (1.8 ± 0.3). Ultimately, CDX1 and CDX2 were upregulated by 1.9 and 4.7-fold, respectively. The above scenario was, variably observed in MKN45 and AGS cells. Conclusion: Our data suggests an interdependent gene regulatory network, induced by H. pylori infection. This interaction begins with the downregulation of RUNX3, upregulation of self-renewal and pluripotency transcription factors, KLF5, SOX2 and SALL4, leading to the downregulation of TNFRSF19, upregulation of LGR5 and aberrant expression of intestine-specific transcription factors, potentially facilitating the process of gastric-to-intestinal transdifferentiation.