Effect of Helicobacter pylori Infection on GATA-5 and TFF1 Regulation, Comparison Between Pediatric and Adult Patients
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GATA factors, which constitute a family of transcription regulatory proteins, participate in gastrointestinal development. Trefoil factor 1 (TFF1) plays a crucial role in mucosal defense and healing, and evidence suggests that GATA-5 mediated its regulation. Gastric cancer is a multiple-step process triggered by Helicobacter pylori and is characterized by accumulation of molecular and epigenetic alteration. The aim of this study was to evaluate the effect of H. pylori infection on the regulation of GATA-5 and TFF1 in vitro and in vivo.
Infected cells exhibited upregulation of GATA-5 and TFF1 after 48 h. An increase in GATA-5 and TFF1 mRNA levels was also found in mice samples after 6 and 12 months of infection, respectively. In human samples, we found an association between H. pylori infection and GATA-5 upregulation. In fact, among H. pylori-infected patients, hypermethylation was observed in 45.5% of pediatric samples, in 62.6% of chronic gastritis samples, and in 63% of gastric cancer samples. Regarding TFF1, the expression levels were similar in pediatrics and adults patients, and were independent of H. pylori infection, and the expression of these factors was downregulated in gastric cancer samples. GATA-5 promoter methylation was associated with a decrease in TFF1 mRNA levels.
Our results suggest that the upregulation of GATA-5 and TFF1 observed in vitro and in vivo may be correlated with a protective effect of the mucosa in response to infection. The epigenetic inactivation of GATA-5 observed in human biopsies from infected patients may suggest that this alteration is an early event occurring in association with H. pylori infection.
KeywordsH. pylori GATA-5 TFF1 DNA methylation
We thank the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (2008/02678-6 and 2011/11224-1) and CNPq for providing financial support.
MCA participated in the design of the study, carried out the bacteria culture, cells culture and co-culture, DNA methylation assay, expression analysis, statistical analysis, and wrote the manuscript. JF participated in cells culture, co-culture, and expression analysis; VM participated in animal infection and RNA extraction; ET and MLR conceived the study, participated in its design and coordination, and helped to draft the manuscript. All authors read and approved the final manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interests.
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