Skip to main content
Top
Published in: BMC Infectious Diseases 1/2018

Open Access 01-12-2018 | Research article

Differential expression of miRNA-146a and miRNA-155 in gastritis induced by Helicobacter pylori infection in paediatric patients, adults, and an animal model

Authors: Ana Caren Cortés-Márquez, Sandra Mendoza-Elizalde, Francisco Arenas-Huertero, Jimena Trillo-Tinoco, Pedro Valencia-Mayoral, Alejandra Consuelo-Sánchez, Jonathan Zarate-Franco, Ada Ruth Dionicio-Avendaño, José de Jesús Herrera-Esquivel, Elio Germán Recinos-Carrera, Christian Colín-Valverde, Sandra Rivera-Gutiérrez, Alfonso Reyes-López, Juan Carlos Vigueras-Galindo, Norma Velázquez-Guadarrama

Published in: BMC Infectious Diseases | Issue 1/2018

Login to get access

Abstract

Background

Helicobacter pylori is a major aetiologic agent associated with gastritis. H. pylori infections increase the expression of the Toll-like receptor (TLR), which in turn modulates the expression of microRNA (miRNA)-146a and miRNA-155. The objective of this study was to compare the expression of miRNA-146a and miRNA-155 in gastric lesions of paediatric and adult patients with different pathologies and in Mongolian gerbils (Meriones unguiculatus) infected with H. pylori 26,695.

Methods

Quantification of miRNA expression was performed by quantitative real-time polymerase chain reaction (qRT-PCR) of paraffin-embedded gastric lesions of children with or without an infection (n = 25), adults with follicular gastritis and metaplasia (n = 32) and eight-week-old M. unguiculatus males (Hsd:MON) infected with H. pylori 26,695 for 0, 3, 6, 12 and 18 months (n = 25). The genes RNU48 and RNU6 were used as endogenous controls for data normalization. Statistical analyses were performed using Kruskal-Wallis, Mann-Whitney, ANOVA and Student’s t-test.

Results

The expression of miRNA-146a and miRNA-155 in infected children increased by 247.6- and 79.4-fold (on average), respectively, compared to that observed in the control group. However, these results were not significant (p = 0.12 and p = 0.07 respectively). In some children a gradual increase in expression was observed, while in others, expression was very high. Additionally, the expression levels of miRNA-146a and miRNA-155 increased by an average of 21.7- and 62-fold, respectively, in adult patients with follicular gastritis when compared to those of the controls. In M. unguiculatus infected with H. pylori 26,695, the expression of both miRNAs increased as the infection progressed.

Conclusion

This is the first report to show differences in the expression of miRNA-146a and miRNA-155 in paediatric and adult patients with gastritis who were infected with H. pylori. In addition, in M. unguiculatus infected with H. pylori, miRNA expression was associated with the progression of infection and the ability of the bacteria to adapt to the host.
Appendix
Available only for authorised users
Literature
1.
go back to reference Sepulveda AR. Helicobacter, inflammation, and gastric Cancer. Curr Pathobiol Rep. 2013;1:9–18.CrossRef Sepulveda AR. Helicobacter, inflammation, and gastric Cancer. Curr Pathobiol Rep. 2013;1:9–18.CrossRef
2.
go back to reference Beltrán-Anaya FO, Manuel Poblete T, Román-Román A, Reyes S, de Sampedro J, Peralta-Zaragoza O, et al. The EPIYA-ABCC motif pattern in CagA of Helicobacter pylori is associated with peptic ulcer and gastric cancer in Mexican population. BMC Gastroenterol. 2014;14:223.CrossRef Beltrán-Anaya FO, Manuel Poblete T, Román-Román A, Reyes S, de Sampedro J, Peralta-Zaragoza O, et al. The EPIYA-ABCC motif pattern in CagA of Helicobacter pylori is associated with peptic ulcer and gastric cancer in Mexican population. BMC Gastroenterol. 2014;14:223.CrossRef
3.
go back to reference Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.CrossRef Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.CrossRef
4.
go back to reference Slezak-Prochazka I, Durmus S, Kroesen BL, van den Berg A. MicroRNAs, macrocontrol: regulation of miRNA processing. RNA. 2010;16:1087–95.CrossRef Slezak-Prochazka I, Durmus S, Kroesen BL, van den Berg A. MicroRNAs, macrocontrol: regulation of miRNA processing. RNA. 2010;16:1087–95.CrossRef
5.
6.
go back to reference Macfarlane LA, Murphy PR. MicroRNA: biogenesis, function and role in Cancer. Curr Genomics. 2010;11:537–61.CrossRef Macfarlane LA, Murphy PR. MicroRNA: biogenesis, function and role in Cancer. Curr Genomics. 2010;11:537–61.CrossRef
7.
go back to reference Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136:215–33.CrossRef Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136:215–33.CrossRef
8.
go back to reference Matsushima K, Isomoto H, Inoue N, Nakayama T, Hayashi T, Nakayama M, et al. MicroRNA signatures in Helicobacter pylori-infected gastric mucosa. Int J Cancer. 2011;128:361–70.CrossRef Matsushima K, Isomoto H, Inoue N, Nakayama T, Hayashi T, Nakayama M, et al. MicroRNA signatures in Helicobacter pylori-infected gastric mucosa. Int J Cancer. 2011;128:361–70.CrossRef
9.
go back to reference Wu F, Zikusoka M, Trindade A, Dassopoulos T, Harris ML, Bayless TM, et al. MicroRNAs are differentially expressed in ulcerative colitis and alter expression of macrophage inflammatory peptide-2 alpha. Gastroenterology. 2008;135:1624–35.CrossRef Wu F, Zikusoka M, Trindade A, Dassopoulos T, Harris ML, Bayless TM, et al. MicroRNAs are differentially expressed in ulcerative colitis and alter expression of macrophage inflammatory peptide-2 alpha. Gastroenterology. 2008;135:1624–35.CrossRef
10.
go back to reference Eulalio A, Schulte L, Vogel J. The mammalian microRNA response to bacterial infections. RNA Biol. 2012;9:742–50.CrossRef Eulalio A, Schulte L, Vogel J. The mammalian microRNA response to bacterial infections. RNA Biol. 2012;9:742–50.CrossRef
11.
go back to reference Staedel C, Darfeuille F. MicroRNAs and bacterial infection. Cell Microbiol. 2013;15:1496–507.CrossRef Staedel C, Darfeuille F. MicroRNAs and bacterial infection. Cell Microbiol. 2013;15:1496–507.CrossRef
12.
go back to reference Zhang, Ying-ke L. MicroRNAs in the regulation of inmune response against infections. J Zhejiang Univ Sci B. 2013;14:1–7.CrossRef Zhang, Ying-ke L. MicroRNAs in the regulation of inmune response against infections. J Zhejiang Univ Sci B. 2013;14:1–7.CrossRef
13.
go back to reference Noto MJ, Peek RM Jr. Helicobacter species. Methods Mol Biol. 2012;921:7–10.CrossRef Noto MJ, Peek RM Jr. Helicobacter species. Methods Mol Biol. 2012;921:7–10.CrossRef
14.
go back to reference Mendoza-Elizalde S, Arteaga-Resendiz NK, Valencia-Mayoral P, Luna RC, Moreno-Espinosa S, Arenas-Huertero F, et al. Diversification of the vacAs1m1 and vacAs2m2 strains of Helicobacter pylori in Meriones unguiculatus. Front Microbiol. 2016;7:1758.CrossRef Mendoza-Elizalde S, Arteaga-Resendiz NK, Valencia-Mayoral P, Luna RC, Moreno-Espinosa S, Arenas-Huertero F, et al. Diversification of the vacAs1m1 and vacAs2m2 strains of Helicobacter pylori in Meriones unguiculatus. Front Microbiol. 2016;7:1758.CrossRef
16.
go back to reference Velazquez-Guadarrama N, Olivares A, Valencia P, De los Monteros L, Madrigal-Santillán E, Madrigal-Bujaidar E. Genotoxic and oxidative damage induced by Helicobacter pylori in Meriones unguiculatus. J Environ Pathol Toxicol Oncol. 2007;26:39–49.CrossRef Velazquez-Guadarrama N, Olivares A, Valencia P, De los Monteros L, Madrigal-Santillán E, Madrigal-Bujaidar E. Genotoxic and oxidative damage induced by Helicobacter pylori in Meriones unguiculatus. J Environ Pathol Toxicol Oncol. 2007;26:39–49.CrossRef
17.
go back to reference Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of gastritis. The updated Sydney system. International workshop on the histopathology of gastritis, Houston 1994. Am J Surg Pathol. 1996;20:1161–81.CrossRef Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of gastritis. The updated Sydney system. International workshop on the histopathology of gastritis, Houston 1994. Am J Surg Pathol. 1996;20:1161–81.CrossRef
18.
go back to reference Akanuma M, Maeda S, Ogura K, Mitsuno Y, Hirata Y, Ikenoue T, Otsuka M, et al. The evaluation of putative virulence factors of Helicobacter pylori for gastroduodenal disease by use of a short-term Mongolian gerbil infection model. J Infect Dis. 2002;185:341–7.CrossRef Akanuma M, Maeda S, Ogura K, Mitsuno Y, Hirata Y, Ikenoue T, Otsuka M, et al. The evaluation of putative virulence factors of Helicobacter pylori for gastroduodenal disease by use of a short-term Mongolian gerbil infection model. J Infect Dis. 2002;185:341–7.CrossRef
19.
go back to reference Nakagawa S, Osaki T, Fujioka Y, Yamaguchi H, Kamiya S. Long-term infection of mongolian gerbils with Helicobacter pylori: microbiological, histopathological, and serological analyses. Clin Diagn Lab Immunol. 2005;12:347–53.PubMedPubMedCentral Nakagawa S, Osaki T, Fujioka Y, Yamaguchi H, Kamiya S. Long-term infection of mongolian gerbils with Helicobacter pylori: microbiological, histopathological, and serological analyses. Clin Diagn Lab Immunol. 2005;12:347–53.PubMedPubMedCentral
20.
go back to reference Smith SI, Oyedeji KS, Arigbabu AO, Cantet F, Megraud F, Ojo OO, et al. Comparison of three PCR methods for detection of Helicobacter pylori DNA and detection of cagA gene in gastric biopsy specimens. World J Gastroenterol. 2004;10:1958–60.CrossRef Smith SI, Oyedeji KS, Arigbabu AO, Cantet F, Megraud F, Ojo OO, et al. Comparison of three PCR methods for detection of Helicobacter pylori DNA and detection of cagA gene in gastric biopsy specimens. World J Gastroenterol. 2004;10:1958–60.CrossRef
22.
go back to reference Liu Z, Tang B, Li B, Li N, Zhu E, et al. Up-regulated microRNA-146a negatively modulate Helicobacter pylori-induced inflammatory response in human gastric epithelial cells. Microbes Infect. 2010;12:854–63.CrossRef Liu Z, Tang B, Li B, Li N, Zhu E, et al. Up-regulated microRNA-146a negatively modulate Helicobacter pylori-induced inflammatory response in human gastric epithelial cells. Microbes Infect. 2010;12:854–63.CrossRef
23.
go back to reference Xiao B, Liu Z, Li BS, Tang B, Li W, Guo G, et al. Induction of microRNA-155 during Helicobacter pylori infection and its negative regulatory role in the inflammatory response. J Infect Dis. 2009;200:916–25.CrossRef Xiao B, Liu Z, Li BS, Tang B, Li W, Guo G, et al. Induction of microRNA-155 during Helicobacter pylori infection and its negative regulatory role in the inflammatory response. J Infect Dis. 2009;200:916–25.CrossRef
24.
go back to reference Matsuura M. Structural modifications of bacterial lipopolysaccharide that facilitate gram-negative bacteria evasion of host innate immunity. Front Immunol. 2013;4:109.CrossRef Matsuura M. Structural modifications of bacterial lipopolysaccharide that facilitate gram-negative bacteria evasion of host innate immunity. Front Immunol. 2013;4:109.CrossRef
25.
go back to reference O’Connell RM, Taganov KD, Boldin MP, Cheng G, Baltimore D. MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci USA. 2007;104:1604–9.CrossRef O’Connell RM, Taganov KD, Boldin MP, Cheng G, Baltimore D. MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci USA. 2007;104:1604–9.CrossRef
26.
go back to reference Michalkiewicz J, Helmin-Basa A, Grzywa R, Czerwionka-Szaflarska M, Szaflarska-Poplawska A, Mierzwa G, et al. Innate Immunity Components and Cytokines in Gastric Mucosa in Children with Helicobacter pylori Infection. Mediators Inflamm. 2015;2015:ID176726:1–7.CrossRef Michalkiewicz J, Helmin-Basa A, Grzywa R, Czerwionka-Szaflarska M, Szaflarska-Poplawska A, Mierzwa G, et al. Innate Immunity Components and Cytokines in Gastric Mucosa in Children with Helicobacter pylori Infection. Mediators Inflamm. 2015;2015:ID176726:1–7.CrossRef
27.
go back to reference Belair C, Baud J, Chabas S, Sharma CM, Vogel J, Staedel C, et al. Helicobacter pylori interferes with an embryonic stem cell micro RNA cluster to block cell cycle progression. Silence. 2011;2:1–7.CrossRef Belair C, Baud J, Chabas S, Sharma CM, Vogel J, Staedel C, et al. Helicobacter pylori interferes with an embryonic stem cell micro RNA cluster to block cell cycle progression. Silence. 2011;2:1–7.CrossRef
28.
go back to reference Gracias DT, Stelekati E, Hope JL, Boesteanu AC, Doering TA, Norton J, et al. The microRNA miR-155 controls CD8(+) T cell responses by regulating interferon signaling. Nat Immunol. 2013;14:593–602.CrossRef Gracias DT, Stelekati E, Hope JL, Boesteanu AC, Doering TA, Norton J, et al. The microRNA miR-155 controls CD8(+) T cell responses by regulating interferon signaling. Nat Immunol. 2013;14:593–602.CrossRef
29.
go back to reference Androulidaki A, Iliopoulos D, Arranz A, Doxaki C, Schworer S, Zacharioudaki V, et al. The kinase Akt1 controls macrophage response to lipopolysaccharide by regulating microRNAs. Immunity. 2009;31:220–31.CrossRef Androulidaki A, Iliopoulos D, Arranz A, Doxaki C, Schworer S, Zacharioudaki V, et al. The kinase Akt1 controls macrophage response to lipopolysaccharide by regulating microRNAs. Immunity. 2009;31:220–31.CrossRef
30.
go back to reference Lario S, Ramírez-Lázaro MJ, Aransay AM, Lozano JJ, Montserrat A, Casalots Á, et al. microRNA profiling in duodenal ulcer disease caused by Helicobacter pylori infection in a Western population. Clin Microbiol Infect. 2012;18:E273–82.CrossRef Lario S, Ramírez-Lázaro MJ, Aransay AM, Lozano JJ, Montserrat A, Casalots Á, et al. microRNA profiling in duodenal ulcer disease caused by Helicobacter pylori infection in a Western population. Clin Microbiol Infect. 2012;18:E273–82.CrossRef
31.
go back to reference Yao Q, Cao Z, Tu C, Zhao Y, Liu H, Zhang S. MicroRNA-146a acts as a metastasis suppressor in gastric cancer by targeting WASF2. Cancer Lett. 2013;335:219–24.CrossRef Yao Q, Cao Z, Tu C, Zhao Y, Liu H, Zhang S. MicroRNA-146a acts as a metastasis suppressor in gastric cancer by targeting WASF2. Cancer Lett. 2013;335:219–24.CrossRef
32.
go back to reference Elton TS, Selemon H, Elton SM, Parinandi NL. Regulation of the MIR155 host gene in physiological and pathological processes. Gene. 2013;532:1–12.CrossRef Elton TS, Selemon H, Elton SM, Parinandi NL. Regulation of the MIR155 host gene in physiological and pathological processes. Gene. 2013;532:1–12.CrossRef
33.
go back to reference Li H, Xie S, Liu M, Chen Z, Liu X, Wang L, et al. The clinical significance of downregulation of miR-124-3p, miR-146a-5p, miR-155-5p and miR-335-5p in gastric cancer tumorigenesis. Int J Oncol. 2014;45:197–208.CrossRef Li H, Xie S, Liu M, Chen Z, Liu X, Wang L, et al. The clinical significance of downregulation of miR-124-3p, miR-146a-5p, miR-155-5p and miR-335-5p in gastric cancer tumorigenesis. Int J Oncol. 2014;45:197–208.CrossRef
34.
go back to reference Sun S, Sun P, Wang C, Sun T. Downregulation of microRNA-155 accelerates cell growth and invasion by targetingc-myc in human gastric carcinoma cells. Oncol Rep. 2014;32:951–6.CrossRef Sun S, Sun P, Wang C, Sun T. Downregulation of microRNA-155 accelerates cell growth and invasion by targetingc-myc in human gastric carcinoma cells. Oncol Rep. 2014;32:951–6.CrossRef
35.
go back to reference Lin CY, Loven J, Rahl PB, Paranal RM, Burge CB, Bradner JE, et al. Transcriptional amplification in tumor cells with elevated c-Myc. Cell. 2012;151:56–67.CrossRef Lin CY, Loven J, Rahl PB, Paranal RM, Burge CB, Bradner JE, et al. Transcriptional amplification in tumor cells with elevated c-Myc. Cell. 2012;151:56–67.CrossRef
36.
go back to reference Hirayama F, Takagi S, Yokoyama Y, Iwao E, Ikeda Y. Establishment of gastric Helicobacter pylori infection in Mongolian gerbils. J Gastroenterol. 1996;31(Suppl 9):24–8.PubMed Hirayama F, Takagi S, Yokoyama Y, Iwao E, Ikeda Y. Establishment of gastric Helicobacter pylori infection in Mongolian gerbils. J Gastroenterol. 1996;31(Suppl 9):24–8.PubMed
37.
go back to reference Philpott DJ, Belaid D, Troubadour P, Thiberge J-M, Tankovic J, Labigne A, et al. Reduced activation of inflammatory responses in host cells by mouse-adapted Helicobacter pylori isolates. Cell Microbiol. 2002;4:285–96.CrossRef Philpott DJ, Belaid D, Troubadour P, Thiberge J-M, Tankovic J, Labigne A, et al. Reduced activation of inflammatory responses in host cells by mouse-adapted Helicobacter pylori isolates. Cell Microbiol. 2002;4:285–96.CrossRef
38.
go back to reference Petrocca F, Visone R, Onelli MR, Shah MH, Nicoloso MS, de Martino I, et al. E2F1-regulated MicroRNAs impair TGF훽-dependent cell-cycle arrest and apoptosis in gastric cancer. Cancer Cell. 2008;13:272–86.CrossRef Petrocca F, Visone R, Onelli MR, Shah MH, Nicoloso MS, de Martino I, et al. E2F1-regulated MicroRNAs impair TGF훽-dependent cell-cycle arrest and apoptosis in gastric cancer. Cancer Cell. 2008;13:272–86.CrossRef
39.
go back to reference Rodriguez A, Vigorito E, Clare S, Warren MV, Couttet P, Soond DR, et al. Requirement of bic/ microRNA-155 for normal immune function. Science. 2007;316:608–11.CrossRef Rodriguez A, Vigorito E, Clare S, Warren MV, Couttet P, Soond DR, et al. Requirement of bic/ microRNA-155 for normal immune function. Science. 2007;316:608–11.CrossRef
40.
go back to reference Chen S, Wang L, Fan J, Ye C, Domiguez D, Zhang Y, et al. Host miR155 promotes tumor growth through a myeloid-derived suppressor cell-dependent mechanism. Cancer Res. 2015;75:519–31.CrossRef Chen S, Wang L, Fan J, Ye C, Domiguez D, Zhang Y, et al. Host miR155 promotes tumor growth through a myeloid-derived suppressor cell-dependent mechanism. Cancer Res. 2015;75:519–31.CrossRef
Metadata
Title
Differential expression of miRNA-146a and miRNA-155 in gastritis induced by Helicobacter pylori infection in paediatric patients, adults, and an animal model
Authors
Ana Caren Cortés-Márquez
Sandra Mendoza-Elizalde
Francisco Arenas-Huertero
Jimena Trillo-Tinoco
Pedro Valencia-Mayoral
Alejandra Consuelo-Sánchez
Jonathan Zarate-Franco
Ada Ruth Dionicio-Avendaño
José de Jesús Herrera-Esquivel
Elio Germán Recinos-Carrera
Christian Colín-Valverde
Sandra Rivera-Gutiérrez
Alfonso Reyes-López
Juan Carlos Vigueras-Galindo
Norma Velázquez-Guadarrama
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2018
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-018-3368-2

Other articles of this Issue 1/2018

BMC Infectious Diseases 1/2018 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine