Analysis of A4gnt Knockout Mice Reveals an Essential Role for Gastric Sulfomucins in Preventing Gastritis Cystica Profunda
| Autor: | Nobuhiko Arisaka, Shigeru Kakuta, Kazuhiro Yamanoi, Hiroto Kawashima, Yoshiko Sato, Chifumi Fujii, Minoru Fukuda, Masaki Miyashita, Satoru Harumiya, Hitomi Komura, Yukinobu Goso, Masatomo Kawakubo, Jun Nakayama, Motohiro Okumura, Shigenori Yamada, Michiko N. Fukuda |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Histology business.industry Hyperplasia medicine.disease Gastric erosion medicine.disease_cause digestive system diseases CXCL1 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Dysplasia 030220 oncology & carcinogenesis Knockout mouse medicine Gastric mucosa Adenocarcinoma Anatomy Carcinogenesis business |
| Zdroj: | Journal of Histochemistry & Cytochemistry. 67:759-770 |
| ISSN: | 1551-5044 0022-1554 |
| DOI: | 10.1369/0022155419860134 |
| Popis: | Gastric adenocarcinoma cells secrete sulfomucins, but their role in gastric tumorigenesis remains unclear. To address that question, we generated A4gnt/ Chst4 double-knockout (DKO) mice by crossing A4gnt knockout (KO) mice, which spontaneously develop gastric adenocarcinoma, with Chst4 KO mice, which are deficient in the sulfotransferase GlcNAc6ST-2. A4gnt/ Chst4 DKO mice lack gastric sulfomucins but developed gastric adenocarcinoma. Unexpectedly, severe gastric erosion occurred in A4gnt/ Chst4 DKO mice at as early as 3 weeks of age, and with aging these lesions were accompanied by gastritis cystica profunda (GCP). Cxcl1, Cxcl5, Ccl2, and Cxcr2 transcripts in gastric mucosa of 5-week-old A4gnt/ Chst4 DKO mice exhibiting both hyperplasia and severe erosion were significantly upregulated relative to age-matched A4gnt KO mice, which showed hyperplasia alone. However, upregulation of these genes disappeared in 50-week-old A4gnt/ Chst4 DKO mice exhibiting high-grade dysplasia/adenocarcinoma and GCP. Moreover, Cxcl1 and Cxcr2 were downregulated in A4gnt/ Chst4 DKO mice relative to age-matched A4gnt KO mice exhibiting adenocarcinoma alone. These combined results indicate that the presence of sulfomucins prevents severe gastric erosion followed by GCP in A4gnt KO mice by transiently regulating a set of inflammation-related genes, Cxcl1, Cxcl5, Ccl2, and Cxcr2 at 5 weeks of age, although sulfomucins were not directly associated with gastric cancer development |
| Databáze: | OpenAIRE |
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