Aim: The main objective of this study was to use high throughput approach to characterize the response of human gastric epithelial cells to Helicobacter pylori (H. pylori) infection at protein level.
Background: Alteration of host cell protein profiles occurs due to H. pylori infection. This alteration seems to be strain specific. High throughput approaches, such as proteomics, can describe changes that occurs at the protein levelin the infected cells in response to H. pylori infection. In accordance with this point of view, we used two dimensional electrophoresis (2-DE)/MS to determine changes in proteome profile of gastric epithelial cells infected with a clinical isolate of H. pylori from an Iranian patient.
Methods: Human gastric epithelial cells (AGS) were infected by an Iranian H. pylori isolate (complete cagPAI, vacA s2m2, babA2, iceA1, sabA). The altered protein patterns separated by 2-DE were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis.
Results: The results showed 40 spots with significantly different intensities between the 2-DE gels. Protein SETSIP and Endoplasmic reticulum resident protein 29 were identified by MALD-TOF and Mascot search. Proteomic analysis for functional roles of these proteins showed that mechanisms to deal with stress conditions and transcriptional activator related to cell reprogramming are involved in H. pylori infection.
Conclusion: Using high throughput approaches, such as proteomics, we can provide further molecular details about interaction of H. pylori strains with the infected cells at protein level.
Graham D. PATHOGENIC MECHANISMS LEADING TO HELICOBACTER-PYLORI-INDUCED INFLAMMATION. European journal of gastroenterology & hepatology. 1992;4:S9-S16.
Vale F, Vítor J. Transmission pathway of Helicobacter pylori: does food play a role in rural and urban areas? International journal of food microbiology. 2010;138(1):1-12.
Ashtari S, Pourhoseingholi MA, Molaei M, Taslimi H, Zali MR. The prevalence of Helicobacter pylori is decreasing in Iranian patients. Gastroenterology and hepatology from bed to bench. 2015;8(Suppl1):S23.
Ashtari S, Pourhoseingholi MA, Molaei M, Zali M. Prevalence of Helicobacter pylori and Intestinal Metaplasia in consecutive gastritis patients; over the period of 7 years. GOVARESH. 2016;21(4):230-7.
Pourhoseingholi MA, Fazeli Z, Ashtari S, Bavand-Pour FSF. Mortality trends of gastrointestinal cancers in Iranian population. Gastroenterology and hepatology from bed to bench. 2013;6(Suppl 1):S52.
Pourhoseingholi M, Moghimi-Dehkordi B, Safaee A, Hajizadeh E, Solhpour A, Zali M. Prognostic factors in gastric cancer using log-normal censored regression model. Indian Journal of Medical Research. 2009;129(3):262.
Pourhoseingholi MA, Vahedi M, Baghestani AR. Burden of gastrointestinal cancer in Asia; an overview. Gastroenterology and hepatology from bed to bench. 2015;8(1):19.
Atherton JC. The pathogenesis of Helicobacter pylori–induced gastro-duodenal diseases. Annu Rev Pathol Mech Dis. 2006;1:63-96.
Cho SO, Lim JW, Jun J-H, Kim KH, Kim H. Helicobacter pylori in a Korean isolate expressed proteins differentially in human gastric epithelial cells. Digestive diseases and sciences. 2010;55(6):1550-64.
Backert S, Gressmann H, Kwok T, Zimny‐Arndt U, König W, Jungblut PR, et al. Gene expression and protein profiling of AGS gastric epithelial cells upon infection with Helicobacter pylori. Proteomics. 2005;5(15):3902-18.
Fazeli Z, Alebouyeh M, Tavirani MR, Azimirad M, Yadegar A. Helicobacter pylori CagA induced interleukin-8 secretion in gastric epithelial cells. Gastroenterology and hepatology from bed to bench. 2016;9(Suppl1):S42.
Margariti A, Winkler B, Karamariti E, Zampetaki A, Tsai T-n, Baban D, et al. Direct reprogramming of fibroblasts into endothelial cells capable of angiogenesis and reendothelialization in tissue-engineered vessels. Proceedings of the National Academy of Sciences. 2012;109(34):13793-8.
Sargsyan E, Baryshev M, Szekely L, Sharipo A, Mkrtchian S. Identification of ERp29, an endoplasmic reticulum lumenal protein, as a new member of the thyroglobulin folding complex. Journal of Biological Chemistry. 2002;277(19):17009-15.
Gibson MC, Perrimon N. Apicobasal polarization: epithelial form and function. Current opinion in cell biology. 2003;15(6):747-52.
Goldstein B, Macara IG. The PAR proteins: fundamental players in animal cell polarization. Developmental cell. 2007;13(5):609-22.
Zhang B, Wang M, Yang Y, Wang Y, Pang X, Su Y, et al. ERp29 is a radiation-responsive gene in IEC-6 cell. Journal of radiation research. 2008;49(6):587-96.
Bullock MD, Sayan AE, Packham GK, Mirnezami AH. MicroRNAs: critical regulators of epithelial to mesenchymal (EMT) and mesenchymal to epithelial transition (MET) in cancer progression. Biology of the Cell. 2012;104(1):3-12.
Sharifian A, Pourhoseingholi MA, Emadedin M, Nejad MR, Ashtari S, Hajizadeh N, et al. Burden of breast cancer in Iranian women is increasing. Asian Pac J Cancer Prev. 2015;16(12):5049-52.
Qi L, Wu P, Zhang X, Qiu Y, Jiang W, Huang D, et al. Inhibiting ERp29 expression enhances radiosensitivity in human nasopharyngeal carcinoma cell lines. Medical oncology. 2012;29(2):721-8.
Zhang D, Putti TC. Over-expression of ERp29 attenuates doxorubicin-induced cell apoptosis through up-regulation of Hsp27 in breast cancer cells. Experimental cell research. 2010;316(20):3522-31.
Bambang I, Lee Y, Richardson D, Zhang D. Endoplasmic reticulum protein 29 regulates epithelial cell integrity during the mesenchymal–epithelial transition in breast cancer cells. Oncogene. 2013;32(10):1240-51.
Bambang IF, Xu S, Zhou J, Salto-Tellez M, Sethi SK, Zhang D. Overexpression of endoplasmic reticulum protein 29 regulates mesenchymal–epithelial transition and suppresses xenograft tumor growth of invasive breast cancer cells. Laboratory investigation. 2009;89(11):1229-42.
Fan N-J, Gao J-L, Liu Y, Song W, Zhang Z-Y, Gao C-F. Label-free quantitative mass spectrometry reveals a panel of differentially expressed proteins in colorectal cancer. BioMed research international. 2015;2015.
Chen S, Zhang D. Friend or foe: Endoplasmic reticulum protein 29 (ERp29) in epithelial cancer. FEBS open bio. 2015;5(1):91-8.
Zhang Y-H, Belegu V, Zou Y, Wang F, Qian B-J, Liu R, et al. Endoplasmic reticulum protein 29 protects axotomized neurons from apoptosis and promotes neuronal regeneration associated with Erk signal. Molecular neurobiology. 2015;52(1):522-32.
Deng Y-J, Tang N, Liu C, Zhang J-Y, An S-L, Peng Y-L, et al. CLIC4, ERp29, and Smac/DIABLO derived from metastatic cancer stem–like cells stratify prognostic risks of colorectal cancer. Clinical Cancer Research. 2014;20(14):3809-17.
White BD, Chien AJ, Dawson DW. Dysregulation of Wnt/β-catenin signaling in gastrointestinal cancers. Gastroenterology. 2012;142(2):219-32.
Oshima H, Matsunaga A, Fujimura T, Tsukamoto T, Taketo MM, Oshima M. Carcinogenesis in mouse stomach by simultaneous activation of the Wnt signaling and prostaglandin E 2 pathway. Gastroenterology. 2006;131(4):1086-95.
Baarsma HA, Königshoff M, Gosens R. The WNT signaling pathway from ligand secretion to gene transcription: molecular mechanisms and pharmacological targets. Pharmacology & therapeutics. 2013;138(1):66-83.
Gao D, Bambang IF, Putti TC, Lee YK, Richardson DR, Zhang D. ERp29 induces breast cancer cell growth arrest and survival through modulation of activation of p38 and upregulation of ER stress protein p58IPK. Laboratory investigation. 2012;92(2):200-13.
Wu C-I, Hoffman JA, Shy BR, Ford EM, Fuchs E, Nguyen H, et al. Function of Wnt/β-catenin in counteracting Tcf3 repression through the Tcf3–β-catenin interaction. Development. 2012;139(12):2118-29.
Yi F, Pereira L, Hoffman JA, Shy BR, Yuen CM, Liu DR, et al. Opposing effects of Tcf3 and Tcf1 control Wnt stimulation of embryonic stem cell self-renewal. Nature cell biology. 2011;13(7):762-70.
Hsieh A, Kim H-S, Lim S-O, Yu D-Y, Jung G. Hepatitis B viral X protein interacts with tumor suppressor adenomatous polyposis coli to activate Wnt/β-catenin signaling. Cancer letters. 2011;300(2):162-72.
Neal JT, Peterson TS, Kent ML, Guillemin K. H. pylori virulence factor CagA increases intestinal cell proliferation by Wnt pathway activation in a transgenic zebrafish model. Disease models & mechanisms. 2013;6(3):802-10.
Kurashima Y, Murata‐Kamiya N, Kikuchi K, Higashi H, Azuma T, Kondo S, et al. Deregulation of β‐catenin signal by Helicobacter pylori CagA requires the CagA‐multimerization sequence. International journal of cancer. 2008;122(4):823-31.
Franco AT, Israel DA, Washington MK, Krishna U, Fox JG, Rogers AB, et al. Activation of β-catenin by carcinogenic Helicobacter pylori. Proceedings of the National Academy of Sciences of the United States of America. 2005;102(30):10646-51.
Suzuki M, Mimuro H, Kiga K, Fukumatsu M, Ishijima N, Morikawa H, et al. Helicobacter pylori CagA phosphorylation-independent function in epithelial proliferation and inflammation. Cell host & microbe. 2009;5(1):23-34.