Helicobacter pylori Containing More Phosphorylation Sites of the CagA Protein Induces Greater Reduction of Gastric Mucins
Moacir Ferreira Júnior
Department of General Pathology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
Sérgio de Assis Batista
Laboratory of Research in Bacteriology, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
Rafael Calvão Barbuto
Department of Surgery, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
Adriana Dias Gomes
Laboratory of Research in Bacteriology, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
Dulciene Maria Magalhães Queiroz
Laboratory of Research in Bacteriology, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
Ivana Duval Araújo
Department of Surgery, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
Marcelo Vidigal Caliari *
Department of General Pathology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
*Author to whom correspondence should be addressed.
Abstract
Aims: H. pylori infection is associated with gastritis, pre cancerous lesions, gastric cancer and changes in the protective layer of mucus. However, to our knowledge, there are no studies in humans or experimental models that relate the infection with H. pylori strains containing one or three phosphorylation sites of the CagA protein with the mucins of the protective layer of mucus. The aim of this study was to research the effects of infection with H. pylori strains containing one or three phosphorylation sites of CagA protein on the MUC1 and MUC5AC mucins of Mongolian gerbils (Meriones unguiculatus) gastric mucosa.
Methods: Mongolian gerbils were inoculated with H. pylori isolates containing one or three EPIYA C phosphorylation sites. The control group consisted of uninfected animals receiving only Brucella broth. Gastric mucosa fragments were assessed by immunohistochemistry using rabbit monoclonal antibodies against MUC1 and MUC5AC. The fragments were then analyzed through a digital morphometric method.
Results: From the control group of non-infected animals (CTRL) to the Cag A positive locci with 1 EPYIA C group (CagA1Ep) and Cag A positive locci with 3 EPYIA C group (CagA3EP) there was a progressive and significant reduction in the expression of both MUC1 (p=0.003) and MUC5AC (p=0.003) after 45 days of infection. This reduction was more prominent in the CagA3Ep group. Similar results were obtained six months post-infection, but the reduction in the MUC5AC (p=0.001) and MUC1 (p=0.001) expression was more intense.
Conclusion: H. pylori strains containing more phosphorylation sites of the CagA protein are able to reduce with greater intensity the expression of MUC1 and MUC5AC.
Keywords: Helicobacter pylori, Mucin-1, Mucin-5AC, CagA protein