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ErbB3 binding protein 1 (EBP1) participates in the regulation of intestinal inflammation via mediating Akt signaling pathway.

Abstract
ErbB3 binding protein-1 (EBP1) belongs to a family of DNA/RNA binding proteins implicated in cell growth, differentiation and apoptosis. Previous data demonstrated that EBP1 regulates phosphorylation of Akt to drive tumor progress. However, the expression and biological functions of EBP1 in ulcerative colitis (UC) remain unclear. In this study, we reported for the first time that EBP1 was down-regulated in intestinal epithelial cell (IECs) of patients with UC. In DSS-induced colitis, we observed the down-regulation of EBP1 accompanied with the elevated levels of proinflammatory cytokines (IL-1β, IL-6 and IL-8) and Akt activation indicators (phosphorylated Akt) in colitis IECs, indicating the possible involvement of EBP1 in regulation of intestinal inflammation via mediating Akt in UC. Employing the TNF-α-treated HT-29 cells as an IEC inflammatory model, we confirmed the negative correlation of EBP1 with Akt activation and Akt-dependent inflammation progress in vitro. EBP1 knocking down and over-expression significantly regulated TNF-α-induced Akt activation and proinflammatory cytokines expression in HT-29 cells. Taken together, our data suggested that EBP1 participates in the regulation of intestinal inflammation via mediating Akt signaling pathway.
AuthorsXianjing Miao, Qiyun Tang, Xiaobing Miao, Yaxun Wu, Ji Qian, Weijuan Zhao, Liang Wang, Liren Li, Dongmei Zhang
JournalMolecular immunology (Mol Immunol) Vol. 67 Issue 2 Pt B Pg. 540-51 (Oct 2015) ISSN: 1872-9142 [Electronic] England
PMID26256794 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier Ltd. All rights reserved.
Chemical References
  • Adaptor Proteins, Signal Transducing
  • PA2G4 protein, human
  • RNA-Binding Proteins
  • Tumor Necrosis Factor-alpha
  • Dextran Sulfate
  • Proto-Oncogene Proteins c-akt
Topics
  • Adaptor Proteins, Signal Transducing (metabolism)
  • Animals
  • Colitis, Ulcerative (chemically induced, metabolism, pathology)
  • Dextran Sulfate
  • Down-Regulation (drug effects)
  • Enterocytes (drug effects, metabolism, pathology)
  • Enzyme Activation (drug effects)
  • Female
  • HT29 Cells
  • Humans
  • Inflammation (metabolism, pathology)
  • Intestines (pathology)
  • Mice, Inbred C57BL
  • Proto-Oncogene Proteins c-akt (metabolism)
  • RNA-Binding Proteins (metabolism)
  • Signal Transduction (drug effects)
  • Tumor Necrosis Factor-alpha (pharmacology)
  • Up-Regulation (drug effects)

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