Intestinal metaplasia with a high salt diet induces epithelial proliferation and alters cell composition in the gastric mucosa of mice

Abstract

Intestinal metaplasia of the gastric mucosa is an important component in the pathway to adenocarcinoma. The mechanisms that induce the progression from intestinal metaplasia to cancer have not been elucidated. High dietary salt has been known as one of the risk factors for gastric cancer development in humans. Therefore, we investigated the role of high salt diet on gastric epithelial cell proliferation and differentiation, using our mouse model that ectopically expressed Cdx2 homeodomain transcription factor and induced an intestinal metaplastic phenotype in the gastric epithelia. Sixty Cdx2 transgenic and sixty age-matched wild-type littermates were studied. Fifty-percent Cdx2 transgenic and wild type mice were administered a high-salt diet and the other fifty-percent was fed a standard diet starting at 12 weeks after birth. At 10, 20 and 40 weeks after initiation of the diets, histopathological changes were determined by Hemotoxylin and Eosin, alcian blue, and periodic acid-Schiff (PAS) staining. Cell types and cell kinetics were assessed by immunohistochemistry. At 52 weeks, significant alterations in pathology were observed in the Cdx2 transgenic mice fed a high-salt diet, including elongation of gastric pits, reduction of the glandular zone in the gastric corpus, and deepening of glands in the antrum. In the Cdx2 transgenic mice fed a high salt diet, the parietal and chief cells were significantly decreased in the gastric corpus. A significant increase in cell proliferation and apoptosis in the corpus and antrum were observed in Cdx2 transgenic mice fed a high-salt diet as compared to wild-type littermates. Taken together, these data implicate that intestinal metaplasia in concert with a high-salt diet induces epithelial proliferation, apoptosis, and alters cellular types in the gastric mucosa of mice. Alteration in the composition of the gastric epithelium may play a role in influencing the microenvironment to engender susceptibility to carcinogens.

High-Salt Diet Has a Certain Impact on Protein Digestion and Gut Microbiota: A Sequencing and Proteome Combined Study

“…Animal studies declared that high-salt diet was regarded to have an adverse effect on gut health, by causing aggravation of tissue inflammation and autoimmune diseases ( Yi et al, 2015 ). Moreover, high-salt diet may cause epithelial proliferation, apoptosis, and altered cellular types ( Xiao et al, 2005 ). Gut microbiota plays an important role in nutritional and immunological processes ( Putignani et al, 2014 ), and changes in the composition of the gut microbiota may have an impact on human health ( Clemente et al, 2012 ).…”

High-Salt Diet Gets Involved in Gastrointestinal Diseases through the Reshaping of Gastroenterological Milieu

“…Alternatively, HSD affects the colonic and small intestine mucosal immunity in mouse models by enhancing the expression of pro-inflammatory genes such as Rac1, Map2k1, Map2k6, Atf2, while suppressing cytokine and chemokine genes like Ccl3, Ccl4, Cxcl2, Cxcr4, Ccr7 [26]. In addition, studies also identified HSD as a risk factor for gastritis in models of mouse and human [7,8], also human functional dyspepsia [27], and gastric cancer of human [28][29][30][31]. High salt intake contributes to gastric toxicity because it decreases the viability of gastric epithelial cells, strips the lining of the stomach, alters the viscosity of the protective mucous barrier, thus permitting the entry of carcinogens into the stomach [29,32,33].…”

High-Salt Diet Exacerbates H. pylori Infection and Increases Gastric Cancer Risks

“…Experimental mice who were given NaCl at high concentrations developed gastric mucosal changes with tissue damage and cell proliferation, leading to gastric cancer [ 34 ]. H. pylori -infected mice were characterized by a loss of parietal cells and hypertrophy of the mucous epithelium in the corpus mucus, compared to the uninfected rodents [ 35 ]. Importantly, those H. pylori -infected mice showed an exacerbation of inflammation with a high salt intake [ 36 ].…”