20557309

pubmed:Citation

8

Helicobacter pylori (H. pylori) stimulates secretion of monocyte chemoattractant protein 1 (MCP-1) from gastric mucosa. Monocyte chemoattractant protein-1 (MCP-1) expression and macrophage infiltration are recognized in human gastric carcinoma. We have previously generated Cdx2-transgenic mice as model mice for intestinal metaplasia. Both chronic H. pylori-associated gastritis and Cdx2-transgenic mouse stomach develop intestinal metaplasia and finally gastric carcinoma. In this study we have directed our attention to MCP-1 expression in the intestinal metaplastic mucosa and the gastric carcinoma of Cdx2-transgenic mouse stomach. Quantitative real-time PCR was performed to determine MCP-1 and transforming growth factor-beta1 (TGF-beta1) mRNA expression levels and single- or double-label immunohistochemistry was used to evaluate the localization of MCP-1, TGF-beta type I receptor, and alpha-smooth muscle actin (alphaSMA). We determined that MCP-1 mRNA dramatically increased in the intestinal metaplastic mucosa and the gastric carcinoma of Cdx2-transgenic mouse stomach, compared with normal mouse stomach. Both MCP-1 and TGF-beta type I receptor were co-expressed in the alphaSMA-positive myofibroblasts of intestinal metaplastic mucosa and gastric carcinoma. Exogenous application of TGF-beta1 increased MCP-1 mRNA expression levels in the intestinal metaplastic tissue. Furthermore, TGF-beta1 was overexpressed and macrophage was strongly infiltrated in the gastric carcinoma. In conclusion, MCP-1 expression, which was stimulated by TGF-beta1, was recognized in the TGF-beta type I receptor-expressing myofibroblasts of the intestinal metaplastic mucosa and the gastric carcinoma of Cdx2-transgenic mouse stomach. The present results suggest that intestinal metaplasia and gastric carcinoma themselves induce MCP-1 expression independently of H. pylori infection.

http://linkedlifedata.com/resource/pubmed/journal/101168776

http://linkedlifedata.com/resource/pubmed/chemical/Actins, http://linkedlifedata.com/resource/pubmed/chemical/Ccl2 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Cdx2 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL2, http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Transforming Growth..., http://linkedlifedata.com/resource/pubmed/chemical/TGF-beta type I receptor, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta1, http://linkedlifedata.com/resource/pubmed/chemical/alpha-smooth muscle actin, mouse

Aug

pubmed-author:HayakawaHirokoH, pubmed-author:MutohHiroyukiH, pubmed-author:SashikawaMihoM, pubmed-author:SuganoKentaroK

101

Y

pubmed-meshheading:20557309-Actins, pubmed-meshheading:20557309-Animals, pubmed-meshheading:20557309-Chemokine CCL2, pubmed-meshheading:20557309-Female, pubmed-meshheading:20557309-Fibroblasts, pubmed-meshheading:20557309-Gastric Mucosa, pubmed-meshheading:20557309-Helicobacter Infections, pubmed-meshheading:20557309-Helicobacter pylori, pubmed-meshheading:20557309-Homeodomain Proteins, pubmed-meshheading:20557309-Immunohistochemistry, pubmed-meshheading:20557309-Macrophages, pubmed-meshheading:20557309-Male, pubmed-meshheading:20557309-Metaplasia, pubmed-meshheading:20557309-Mice, pubmed-meshheading:20557309-Mice, Transgenic, pubmed-meshheading:20557309-Protein-Serine-Threonine Kinases, pubmed-meshheading:20557309-Receptors, Transforming Growth Factor beta, pubmed-meshheading:20557309-Stomach Neoplasms, pubmed-meshheading:20557309-Transcription Factors, pubmed-meshheading:20557309-Transforming Growth Factor beta1

Monocyte chemoattractant protein-1 is generated via TGF-beta by myofibroblasts in gastric intestinal metaplasia and carcinoma without H. pylori infection.

Journal Article