論文

査読有り 国際誌
2019年10月

Analysis of A4gnt Knockout Mice Reveals an Essential Role for Gastric Sulfomucins in Preventing Gastritis Cystica Profunda.

The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society
  • Masatomo Kawakubo
  • ,
  • Hitomi Komura
  • ,
  • Yukinobu Goso
  • ,
  • Motohiro Okumura
  • ,
  • Yoshiko Sato
  • ,
  • Chifumi Fujii
  • ,
  • Masaki Miyashita
  • ,
  • Nobuhiko Arisaka
  • ,
  • Satoru Harumiya
  • ,
  • Kazuhiro Yamanoi
  • ,
  • Shigenori Yamada
  • ,
  • Shigeru Kakuta
  • ,
  • Hiroto Kawashima
  • ,
  • Michiko N Fukuda
  • ,
  • Minoru Fukuda
  • ,
  • Jun Nakayama

67
10
開始ページ
759
終了ページ
770
記述言語
英語
掲載種別
DOI
10.1369/0022155419860134

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.

リンク情報
DOI
https://doi.org/10.1369/0022155419860134
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31246144
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764063

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