Site-specific induction of intestinal hypoxia-inducible factor-1α after hemorrhagic shock

Hiroyuki Nishie, Toru Takahashi, Kazuyoshi Inoue, Hiroko Shimizu, Hiroshi Morimatsu, Yuichiro Toda, Emiko Omori, Reiko Akagi, Hiroshi Katayama, Kiyoshi Morita

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1 Citation (Scopus)

Abstract

The intestine is a major target organ in hemorrhagic shock (HS)-induced tissue injury. Hypoxia-inducible factor (HIF)-1α is the primary transcription factor responsible for regulating cellular response to changes in oxygen tension. Since HS is an acute hypoxic insult, the present study examined changes in the gene expression of HIF-1α in various regions of the intestine, as well as the distribution of HIF-1α protein in the intestinal cells of a rat model of HS. Levels of HIF-1α mRNA were marginally detectable in the intestine of sham-operated control animals, but obviously induced following HS. Duodenal, jejunal and colonic levels of HIF-1α mRNA robustly increased and reached a maximum during the ischemic phase of HS, followed by a rapid decrease almost to control levels during the early phase of resuscitation. The induction of HIF-1α mRNA was maximal in the duodenum. In contrast to the duodenum, jejunum and colon, in the ileum the HIF-1α mRNA level did not increase after HS. Consistent with enhanced HIF-1α gene expression, HIF-1α protein was expressed in the mucosal cells of the duodenum, jejunum and colon, but not in the ileum following HS. These findings indicate that intestinal HIF-1α expression was up-regulated at both the transcriptional and protein level in a site-specific manner in this rat model of HS. Differential regulation of HIF-1α expression along the longitudinal axes of the intestine might be a determinant of the adaptive response to HS-induced intestinal damage.

Original languageEnglish
Pages (from-to)149-152
Number of pages4
JournalMolecular Medicine Reports
Volume2
Issue number2
DOIs
Publication statusPublished - Aug 31 2009

Keywords

  • Hypoxic insult
  • Intestine
  • Multiple organ failure
  • Systemic inflammation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Oncology
  • Cancer Research

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  • Cite this

    Nishie, H., Takahashi, T., Inoue, K., Shimizu, H., Morimatsu, H., Toda, Y., Omori, E., Akagi, R., Katayama, H., & Morita, K. (2009). Site-specific induction of intestinal hypoxia-inducible factor-1α after hemorrhagic shock. Molecular Medicine Reports, 2(2), 149-152. https://doi.org/10.3892/mmr-00000075