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P. gingivalis Lipopolysaccharide Stimulates the Upregulated Expression of the Pancreatic Cancer-Related Genes Regenerating Islet-Derived 3 A/G in Mouse Pancreas

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Division of Reconstructive Surgery for Oral and Maxillofacial Region, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan
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Division of Disease Control and Molecular Epidemiology, Department of Oral Growth and Development, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan
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Research Institute of Cancer Prevention, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan
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Division of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan
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Division of Oral and Maxillofacial Surgery, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(19), 7351; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21197351
Received: 4 September 2020 / Revised: 1 October 2020 / Accepted: 1 October 2020 / Published: 5 October 2020
(This article belongs to the Section Molecular Genetics and Genomics)
Although epidemiological studies have shown a relationship between periodontal disease and pancreatic cancer, the molecular mechanisms involved remain unclear. In this study, the effects of systemic administration of Porphyromonas gingivalis lipopolysaccharide (PG-LPS) on gene expression were comprehensively explored in mouse pancreas that did not demonstrate any signs of inflammation. PG-LPS was prepared in physiological saline and intraperitoneally administered to male mice at a concentration of 5 mg/kg every 3 days for 1 month. After extracting total RNA from the excised mice pancreas, a comprehensive DNA microarray analysis of gene expression was performed. Tissue specimens were also subjected to hematoxylin–eosin staining and immunohistochemistry using anti-regenerating islet-derived 3A and G (Reg3A/G) antibody. ImageJ software was used to quantify the area of Reg3A/G positive cells in pancreatic islets by binarizing image date followed by area extraction. The results were compared using Mann–Whitney U test. Data are presented as mean ± standard deviation (SD) with p < 0.05 considered as significant. Reg3G, a gene related to pancreatic cancer, was one of the 10 genes with the highest levels of expression in the pancreas stimulated with PG-LPS. The comprehensive analysis revealed a 73-fold increase in Reg3G expression level in the PG-LPS group when compared with the control group; in addition, the expression level of Reg3A was increased by 11-fold in the PG-LPS group. Image analysis showed that the ratio of Reg3A/G positive cells was higher in the PG-LPS group than the control. Immunostaining showed the presence of Reg3A/G-positive cells in the alpha-cell equivalent areas around the islets of Langerhans in the PG-LPS group. These results support the notion that periodontal disease may be a risk factor for pancreatic cancer. View Full-Text
Keywords: P. gingivalis; lipopolysaccharide; pancreatic cancer; Reg3G P. gingivalis; lipopolysaccharide; pancreatic cancer; Reg3G
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MDPI and ACS Style

Hiraki, D.; Uehara, O.; Kuramitsu, Y.; Morikawa, T.; Harada, F.; Yoshida, K.; Akino, K.; Chiba, I.; Asaka, M.; Abiko, Y. P. gingivalis Lipopolysaccharide Stimulates the Upregulated Expression of the Pancreatic Cancer-Related Genes Regenerating Islet-Derived 3 A/G in Mouse Pancreas. Int. J. Mol. Sci. 2020, 21, 7351. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21197351

AMA Style

Hiraki D, Uehara O, Kuramitsu Y, Morikawa T, Harada F, Yoshida K, Akino K, Chiba I, Asaka M, Abiko Y. P. gingivalis Lipopolysaccharide Stimulates the Upregulated Expression of the Pancreatic Cancer-Related Genes Regenerating Islet-Derived 3 A/G in Mouse Pancreas. International Journal of Molecular Sciences. 2020; 21(19):7351. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21197351

Chicago/Turabian Style

Hiraki, Daichi, Osamu Uehara, Yasuhiro Kuramitsu, Tetsuro Morikawa, Fumiya Harada, Koki Yoshida, Kozo Akino, Itsuo Chiba, Masahiro Asaka, and Yoshihiro Abiko. 2020. "P. gingivalis Lipopolysaccharide Stimulates the Upregulated Expression of the Pancreatic Cancer-Related Genes Regenerating Islet-Derived 3 A/G in Mouse Pancreas" International Journal of Molecular Sciences 21, no. 19: 7351. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21197351

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