Repressed TGF-β signaling through CagA-Smad3 interaction as pathogenic mechanisms of <i>Helicobacter pylori</i>-associated gastritis

• Nguyen Thuy Trang

  Laboratory of Chemoprevention, Lee Gil Ya Cancer and Diabetes Institute, Gachon University

• Kim Seong-Jin

  CHA University Cancer Prevention Research Center, CHA Bio Complex

• Park Jong Min

  CHA University Cancer Prevention Research Center, CHA Bio Complex

• Hahm Ki Baik

  CHA University Cancer Prevention Research Center, CHA Bio Complex

• Lee Ho-Jae

  Laboratory of Chemoprevention, Lee Gil Ya Cancer and Diabetes Institute, Gachon University

抄録

Helicobacter pylori (H. pylori) infection causes chronic gastric inflammation, peptic ulceration, and gastric carcinogenesis, in which H. pylori cytotoxin-associated gene A (CagA) plays major pathogenic action. Since transforming growth factor-β (TGF-β) and its signaling also are principally implicated in either modulating gastric mucosal inflammatory responses or causing carcinogenesis and are attenuated after H. pylori infection, we hypothesized that dysregulated Smad signaling and repressed TGF-β might be core pathogenic mechanism for H. pylori-associated gastritis or carcinogenesis. Until now, no precise underlying mechanism how deranged TGF-β signaling developed after H. pylori infection relevant to various clinical manifestations remains unclear. In this study, we examined the molecular mechanism about the inhibition of TGF-β signaling by H. pylori CagA protein. H. pylori CagA significantly suppressed TGF-β/Smad transcriptional responses through critical inhibition of Smad3, though CagA interacted constitutively with Smad2, Smad3, and Smad4. CagA inhibited TGF-β-induced suppression of proinflammatory chemokines, such as IL-8, CXCL1 and CXCL3, as well as TGF-β-induced transcription of target genes. In conclusion, repressed TGF-β signaling associated with CagA-positive H. pylori infection could be an important determinant for the outcome of H. pylori infection. Therefore, TGF-β signaling is one of the important determinants to avoid from H. pylori CagA pathogenicity.

収録刊行物

• Ｊｏｕｒｎａｌ　ｏｆ　Ｃｌｉｎｉｃａｌ　Ｂｉｏｃｈｅｍｉｓｔｒｙ　ａｎｄ　Ｎｕｔｒｉｔｉｏｎ

  Ｊｏｕｒｎａｌ　ｏｆ　Ｃｌｉｎｉｃａｌ　Ｂｉｏｃｈｅｍｉｓｔｒｙ　ａｎｄ　Ｎｕｔｒｉｔｉｏｎ 57 (2), 113-120, 2015

  一般社団法人　日本酸化ストレス学会

キーワード

• <i>Helicobacter pylori</i>
• Cytotoxin-associated gene A
• TGF-β
• Smad
• inflammation

詳細情報

• CRID: 1390001204671685504
• NII論文ID: 130005096233
• DOI: 10.3164/jcbn.15-38
• ISSN: 18805086
• ISSN: 09120009
• Web Site: https://www.jstage.jst.go.jp/article/jcbn/57/2/57_15-38/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2016175240
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可