Enterocyte apoptosis after enterectomy in mice is activated independent of the extrinsic death receptor pathway

Andrew W. Knott, David P. O'Brien, Russell J. Juno, Yufang Zhang, Jodi L. Williams, Christopher R. Erwin, Brad W. Warner

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Intestinal adaptation following small bowel resection (SBR) is associated with greater rates of enterocyte apoptosis by unknown mechanism(s). Because postresection adaptation is associated with increased translocation of luminal bacteria, we sought to characterize the role for the extrinsic, death receptor pathway for the activation of enterocyte apoptosis after massive SBR. We first performed SBR or sham operations in mice, and the temporal expression of caspases 8, 9, and 3, death receptors tumor necrosis factor receptor-1 (TNFR1) and Fas and corresponding ligands (TNF and Fas ligand) was determined in the remnant intestine at various postoperative time points. Ileal TNFR1 and Fas expression were then measured after SBR in the setting of increased (waved-2 mice) or decreased (exogenous EGF administration) apoptosis. Finally, intestinal adaptation and apoptosis were recorded in the remnant ileum after SBR in TNFR1-null and Fas-null mice. The expression of death receptor family proteins and caspases demonstrated only modest changes after SBR and did not correlate with the histological appearance of apoptosis. In the setting of accelerated apoptosis, TNFR1 and Fas expression were paradoxically decreased. Apoptotic and adaptive responses were preserved in both TNFR1-null and Fas-null mice. These results suggest that the mechanism for increased enterocyte apoptosis following massive SBR does not appear to involve the extrinsic, death receptor-mediated pathway.

Original languageEnglish
Pages (from-to)G404-G413
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume285
Issue number2 48-2
StatePublished - Aug 1 2003
Externally publishedYes

Keywords

  • Fas
  • Intestinal adaptation
  • Intestinal mucosa
  • Short bowel syndrome
  • Tumor necrosis factor receptor

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