Study of the correlation between the expression of nuclear factor kappa B and proliferation regulatory proteins and chronic superficial gastritis

Hui Hu; Zhijian Ma; Shouzhong Ren; Yiqiang Xie

doi:10.2298/VSP200807135H

Hui Hu Hainan University, Faculty of Chemical Engineering and Technology, Haikou, China
Zhijian Ma Hainan Medical University, Faculty of Pharmacy, Haikou, China
Shouzhong Ren Hainan Medical University, Faculty of Pharmacy, Haikou, China
Yiqiang Xie Hainan Medical University, College of Traditional Chinese Medicine, Haikou, China

DOI: https://doi.org/10.2298/VSP200807135H

Keywords: antigens, nuclear, cell proliferation, dna-binding proteins, epidermal factor growth, gastritis, immunohistochemistry, rats

Abstract

Background/Aim. Cell proliferation and the regulation of protein expression play an important role in gastritis, but in chronic superficial gastritis (CSG), they are rarely reported. The aim of this study was to determine the relationship between the expression of nuclear factor kappa B (NF-κB) and regulatory proteins and the rat CSG. Methods. The CSG rat model was established artificially, by chemical agents and irregular diet. The expression of epidermal growth factor receptor (EGFR) and proliferating cell nuclear antigen (PCNA) in the gastric mucosa of CSG rats was measured by immunohistochemistry, while mRNA expression levels of NF-κB p65 were detected by in situ hybridization. Results. There was more obvious infiltration of inflammatory cells in the gastric mucosa of CSG rats than in that of control rats, and the inflammation score was significantly increased. The expression levels of PCNA, EGFR, and NF-κB p65 mRNA in the gastric mucosal cells of CSG model rats increased significantly. Correlation analysis showed that the inflammation score was positively correlated with the expression levels of NF-κB p65 mRNA and EGFR, while it presented no significant correlation with the expression level of PCNA. In addition, there was a significant positive correlation between NF-κB p65 mRNA and EGFR levels. Conclusion. High expression of NF-κB and EGFR plays an important role in the occurrence and progression of CSG, and it is significantly positively correlated with the degree of inflammation in the gastric mucosa. Therefore, changes in NF-κB and EGFR expression may be used as important indicators for the assessment of CSG; changes in their expression levels are helpful to assess the degree of gastric mucosal lesions and progression of CSG.

References

Sipponen P, Maaroos HI. Chronic gastritis. Scand J Gastroenter-ol 2015; 50(6): 657–67.

Varis K, Sipponen P, Laxen F, Samloff IM, Huttunen JK, Taylor PR, et al. Implications of serum pepsinogen I in early endoscopic diagnosis of gastric cancer and dysplasia. The Helsinki Gastritis Study Group. Scand J Gastroenterol 2000, 35(9): 950–6.

Lin HY, Zhao Y, Yu JN, Jiang WW, Sun XL. Effects of tradi-tional Chinese medicine Wei-Wei-Kang-Granule on the ex-pression of EGFR and NF-kB chronic atrophic gastritis rats. Afr J Tradit Complement Altern Med 2012; 9(1): 1‒7.

Chen XY, Zou SJ. Pathological Changes of Gastric Mucosal in Rat Models of Combined CAG Syndrome and Disease. J Shanghai Labo Ani Sci 2002; 20: 292‒6.

Lauwers G. Epithelial neoplasms of the stomach. In: Odze R, Goldblum J, editors. Surgical Pathology of the GI Tract, Liver, Biliary Tract, and Pancreas. 2nd ed. Philadelphia: Saunders Elsevier; 2009. p. 564–72.

Oguma K, Oshima H, Oshima M. Inflammation, tumor necrosis factor and Wnt promotion in gastric cancer development. Fu-ture Oncol 2010; 6(4): 515–26.

Oshima H, Ishikawa T, Yoshida GJ, Naoi K, Maeda Y, Naka K, et al. TNF-a/TNFR1 signaling promotes gastric tumorigenesis through induction of Noxo1 and Gna14 in tumor cells. Onco-gene 2014, 33(29): 3820–9.

Putoczki TL, Thiem S, Loving A, Busuttil RA, Wilson NJ, Ziegler PK, et al. Interleukin-11 is the dominant IL-6 family cytokine during gastrointestinal tumorigenesis and can be targeted ther-apeutically. Cancer Cell 2013, 24(2): 257–71.

Kulmambetova GN, Imanbekova MK, Logvinenko AA, Sukashev AT, Filipenko ML, Ramanculov EM. Association of Cytokine Gene Polymorphisms with Gastritis in a Kazakh Population. Asian Pac J Cancer Prev 2014; 15(18): 7763‒8.

Li WF, Hao DJ, Fan T, Huang HM, Yao H, Niu XF. Protective effect of chelerythrine against ethanol-induced gastric ulcer in mice. Chem Biol Interact 2014; 208: 18–27.

Ritter B, Kilian P, Reboll MR, Resch K, Distefano JK, Frank R, et al. Differential effects of multiplicity of infection on Helico-bacter pylori-induced signaling pathways and interleukin-8 gene transcription. J Clin Immunol 2011; 31(1): 60‒8.

Altavilla D, Saitta A, Guarini S, Galeano M, Squadrito G, Cucinotta D, et al. Oxidative stress causes nuclear factor-kappa B activation in acute hypovolemic hemorrhagic shock. Free Radic Biol Med 2001; 30(10): 1055‒66.

Barnes PJ, Karin M. Nuclear factor-κB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med 1997; 336(15): 1066‒71.

Yanai A, Maeda S, Shibata W, Hikiba Y, Sakamoto K, Nakagawa H, et al. Activation of kappaB kinase and NF-kappaB is essen-tial for Helicobacter pylori-induced chronic gastritis in Mon-golian gerbils. Infect Immun 2008; 76(2): 781‒7.

Cui NJ, Hu L, Lao SX. Relationship between Pi-Wei damp-heat syndrome with expression of nuclear factor-mRNA and heat shock protein 70 mRNA in patients with chronic gastri-tis. Zhongguo Zhong Xi Yi Jie He Za Zhi 2010; 30(1): 18‒21. (Chinese)

Tu S, Bhagat G, Cui G, Takaishi S, Kurt-Jones EA, Rickman B, et al. Overexpression of interleukin-1beta induced gastric in-flammation and cancer and mobilizes myeloid-derived sup-pressor cells in mice. Cancer Cell 2008; 14(5): 408–19.

van den Brink GR, ten Kate FJ, Ponsioen CY, Rive MM, Tytgat GN, van Deventer SJ, et al. Expression and Activation of NF-kB in the Antrum of the Human Stomach. J Immunol 2000; 164(6): 3353‒9.

Doger FK, Meteoglu I, Ozkara E, Erkul ZK，Okyay P，Yukselen V. Expression of NF-κB in Helicobacter pylori Infection. Dig Dis Sci 2006; 51(12): 2306‒9.

Moorchung N, Srivastava AN, Sharma AK, Achyut BR, Mittal B. Nuclear factor kappa-B and histopathology of chronic gastri-tis. Indian J Pathol Microbiol 2010; 53(3): 418‒24.

Moorchung N, Srivastava AN, Gupta NK, Ghoshal UC, Achyut BR, Mittal B. Cytokine gene polymorphisms in the pathogene-sis of chronic gastritis. Singapore Med J 2007; 48(5): 447‒54.

Jurkowska G, Piotrowska-Staworko G, Guzinska-Ustymowicz K, Kemona A, Świdnicka-Siergiejko A, Łaszewicz W, et al. The impact of helicobacter pylori on EGF, EGF receptor, and the c-erb-B2 expression. Adv Med Sci 2014; 59(2): 221‒6.

Yan F, Cao H, Chaturvedi R, Krishna U, Hobbs SS, Dempsey PJ, et al. Epidermal growth factor receptor activation protects gastric epithelial cells from Helicobacter pylori-induced apop-tosis. Gastroenterology 2009; 136(4): 1297‒307, e1‒3.

Shimamoto C, Hirata I, Umegaki E, Takiuchi H, Hiraike Y, Fuji-wara S, et al. Gastric mucosal cell protection by epidermal growth factor in primary monolayer culture of guinea pig gas-tric mucous cells. J Gastroenterol 2003; 38(8): 727‒33.

Ichikawa T, Endoh H, Hotta K, Ishihara K. The mucin biosynthe-sis stimulated by epidermal growth factor occurs in surface mucus cells, but not in gland mucus cells, of rats stomach. Life Sci 2000; 67(9): 1095‒101.

Mendelsohn J. Targeting the epidermal growth factor receptor for cancer therapy. J Clin Oncol 2002; 20(18 Suppl): 1S‒13S.

Moutinho C, Mateus AR, Milanezi F, Carneiro F, Seruca R, Suri-ano G. Epidermal growth factor receptor structural alterations in gastric cancer. BMC Cancer 2008; 8: 10.

Kim MA, Lee HS, Lee HE, Jeon YK, Yang HK, Kim WH. EGFR in gastric carcinomas: prognostic significance of pro-tein overexpression and high gene copy number. Histopathol-ogy 2008; 52(6): 738‒46.

Agréus L, Kuipers EJ, Kupcinskas L, Malfertheiner P, Di Mario F, Leja M, et al. Rationale in diagnosis and screening of atrophic gastritis with stomach-specific plasma biomarkers. Scand J Gastroenterol 2012; 47(2): 136‒47.

Rossi E, Villanacci V, Danesino C, Donato F, Nascimbeni R, Bas-sotti G. Epidermal growth factor receptor overexpres-sion/amplification in adenocarcinomas arising in the gastroin-testinal tract. Rev Esp Enferm Dig 2011; 103(12): 632‒9.

Hofmann M, Stoss O, Shi D, Büttner R, van de Vijver M, Kim W, et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology 2008; 52(7): 797‒805.

Jiang L, Lan T, Chen YC, Sang JR, Li Y, Wu M, et al. PKG II inhibits EGF/EGFR-induced migration of gastric cancer cells. PLoS One 2013; 8(4): e61674.

Mitsui F, Dobashi Y, Imoto I, Inazawa J, Kono K, Fujii H, et al. Non-incidental coamplification of Myc and ERBB2, and Myc and EGFR in gastric adenocarcinoma. Mod Pathol 2007; 20(6): 622‒31.

Kimura T, Maesawa C, Ikeda K, Wakabayashi G, Masuda T. Mutations of the epidermal growth factor receptor gene in gastrointestinal tract tumor cell lines. Oncol Rep 2006; 15(5): 1205‒10.

Kimura M, Tsuda H, Morita D, Shinto E, Tanimoto T, Ichikura T, et al. Usefulness and limitation of multiple en-doscopic biopsy sampling for epidermal growth factor receptor and c-erbB-2 testing in patients with gastric adenocarcinoma. Jpn J Clin Oncol 2005; 35(6): 324‒31.

Oshima H, Papivanova BK, Oguma K, Kong D, Ishikawa TO, Oshima M. Activation of epithelial growth factor receptor sig-naling by the prostaglandin E2 receptor EP4 pathway during gastric tumorigenesis. Cancer Sci 2011; 102(4): 713‒9

Hynes NE, Lane HA. ERBB receptors and cancer: The com-plexity of targeted inhibitors. Nat Rev Cancer 2005; 5(5): 341–54.

Wang YL, Sheu BS, Yang HB, Lin PW, Chang YC. Overexpres-sion of c-erb-B2 proteins in tumor and non-tumor parts of gastric adenocarcinoma-emphasis on its relation to H. pylori infection and clinicohistological characteristics. Hepatogastro-enterology 2002; 49(46): 1172‒6.

Miyachi K, Fritzler MJ, Tan EM. Autoantibody to a nuclear an-tigen in proliferating cells. J Immunol 1978; 121(6): 2228–34.

Prelich G, Tan CK, Kostura M, Mathews MB, So AG, Downey KM, et al. Functional identity of proliferating cell nuclear antigen and a DNA polymerase-delta auxiliary protein. Nature 1987; 326(6112): 517‒20.

Moldovan GL, Pfander B, Jentsch S. PCNA, the maestro of the replication fork. Cell 2007; 129(4): 665‒79.

Liu ZX, Chen BW, Yang GB, Liu P, Zhang XQ, Li J, et al. Pro-liferative changes of human gastric mucosa cells in different pathological lesions and their clinical significance. Zhonghua Nei Ke Za Zhi 2004; 43(8): 580‒3. (Chinese).