Effect of Helicobacter pylori Infection on GATA-5 and TFF1 Regulation, Comparison Between Pediatric and Adult Patients

Autor(es)

Alvarez, Marisa Claudia ^{[1, 2]} ; Fernandes, Julien ^[3] ; Michel, Valerie ^[3] ; Touati, Eliette ^[3] ; Ribeiro, Marcelo Lima ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Programa Pos Grad Genet & Biol Mol, Campinas, SP - Brazil

^[2] Univ Sao Francisco, Programa Pos Grad Ciencias Saude, Av Sao Francisco Assis, 218 Jd Sao Jose, BR-12196900 Braganca Paulista, SP - Brazil

^[3] Inst Pasteur, Unite Pathogenese Helicobacter, Paris - France

• Tipo de documento: Artigo Científico
• Fonte: Digestive Diseases and Sciences; v. 63, n. 11, p. 2889-2897, NOV 2018.
• Citações Web of Science: 3

Resumo

BackgroundGATA 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.ResultsInfected cells exhibited upregulation of GATA-5 and TFF1 after 48h. An increase in GATA-5 and TFF1 mRNA levels was also found in mice samples after 6 and 12months 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.ConclusionsOur 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. (AU)

• Processo FAPESP: 08/02678-6 - ANÁLISE DA INFLUÊNCIA DO Helicobacter pylori NO PADRÃO DE METILAÇÃO DE GENES RELACIONADOS AO MECANISMO DE REPARO AO DNA E NA INSTABILIDADE DE MICROSSATÉLITES
• Beneficiário: Marisa Claudia Alvarez de Prax
• Linha de fomento: Bolsas no Brasil - Doutorado
• Processo FAPESP: 11/11224-1 - Análise da influência da infecção por Helicobacter pylori na modulação de mecanismos epigenéticos relacionados aos sistemas de reparo ao DNA
• Beneficiário: Marcelo Lima Ribeiro
• Linha de fomento: Auxílio à Pesquisa - Regular