TGF-β-activated kinase 1 signaling maintains intestinal integrity by preventing accumulation of reactive oxygen species in the intestinal epithelium

Rie Kajino-Sakamoto, Emily Omori, Prashant Nighot, Anthony T. Blikslager, Kunihiro Matsumoto, Jun Ninomiya-Tsuji

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The intestinal epithelium is constantly exposed to inducers of reactive oxygen species (ROS), such as commensal microorganisms. Levels of ROS are normally maintained at nontoxic levels, but dysregulation of ROS is involved in intestinal inflammatory diseases. In this article, we report that TGF-β-activated kinase 1 (TAK1) is a key regulator of ROS in the intestinal epithelium. tak1 gene deletion in the mouse intestinal epithelium caused tissue damage involving enterocyte apoptosis, disruption of tight junctions, and inflammation. Disruption of TNF signaling, which is a major intestinal damage inducer, rescued the inflammatory conditions but not apoptosis or disruption of tight junctions in the TAK1-deficient intestinal epithelium, suggesting that TNF is not a primary inducer of the damage noted in TAK1-deficient intestinal epithelium. We found that TAK1 deficiency resulted in reduced expression of several antioxidant-responsive genes and reduced the protein level of a key antioxidant transcription factor NF-E2-related factor 2, which resulted in accumulation of ROS. Exogenous antioxidant treatment reduced apoptosis and disruption of tight junctions in the TAK1-deficient intestinal epithelium. Thus, TAK1 signaling regulates ROS through transcription factor NF-E2-related factor 2, which is important for intestinal epithelial integrity.

Original languageEnglish (US)
Pages (from-to)4729-4737
Number of pages9
JournalJournal of Immunology
Volume185
Issue number8
DOIs
StatePublished - Oct 15 2010

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Intestinal Mucosa
Reactive Oxygen Species
Phosphotransferases
Tight Junctions
NF-E2-Related Factor 2
Antioxidants
Apoptosis
Transcription Factors
Intestinal Diseases
Enterocytes
Gene Deletion
Inflammation
Proteins

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Kajino-Sakamoto, Rie ; Omori, Emily ; Nighot, Prashant ; Blikslager, Anthony T. ; Matsumoto, Kunihiro ; Ninomiya-Tsuji, Jun. / TGF-β-activated kinase 1 signaling maintains intestinal integrity by preventing accumulation of reactive oxygen species in the intestinal epithelium. In: Journal of Immunology. 2010 ; Vol. 185, No. 8. pp. 4729-4737.
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TGF-β-activated kinase 1 signaling maintains intestinal integrity by preventing accumulation of reactive oxygen species in the intestinal epithelium. / Kajino-Sakamoto, Rie; Omori, Emily; Nighot, Prashant; Blikslager, Anthony T.; Matsumoto, Kunihiro; Ninomiya-Tsuji, Jun.

In: Journal of Immunology, Vol. 185, No. 8, 15.10.2010, p. 4729-4737.

Research output: Contribution to journalArticle

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