HSP-dependent protection against gastrointestinal diseases

Tohru Mizushima

Research output: Contribution to journalReview article

14 Citations (Scopus)

Abstract

It is well known that heat shock proteins (HSPs) are induced by various stressors in order to confer protection against such stressors. Since stressor-induced tissue damage is involved in various diseases, especially gastrointestinal diseases, such as gastric ulcer, it has been thought that HSPs are protective against these diseases. Indirect lines of evidence, such as identification of geranylgeranylacetone (GGA, a leading anti-ulcer drug in Japanese market) as non-toxic HSP-inducer, suggest that HSPs provide a major protective mechanism against irritant-induced gastric lesions. However, no direct evidences that support this notion exits. Furthermore, because GGA has other gastroprotective effects, it was not clear whether HSP-induction by GGA is the main mechanism for its anti-ulcer effect. In this article, I review our recent work on protective roles of HSPs against gastrointestinal diseases, using transgenic mice. We obtained genetic evidence showing not only that HSPs are protective against irritant-induced gastric lesions but also that GGA achieves its anti-ulcer effect through induction of HSPs. We also obtained genetic evidence that HSPs are protective against inflammatory bowel disease (IBD)-related colitis and lesions of small intestine. Furthermore, we found that GGA is effective against these diseases. Based on these observations, we propose that non-toxic HSP-inducers, such as GGA are therapeutically beneficial for these diseases.

Original languageEnglish
Pages (from-to)1190-1196
Number of pages7
JournalCurrent Pharmaceutical Design
Volume16
Issue number10
DOIs
Publication statusPublished - 2010 Apr 1

Keywords

  • GGA
  • Gastric ulcer
  • HSF1
  • HSP70
  • IBD
  • Lesions of the small intestine

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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