Absent STAT-1 expression perturbs adaptation and apoptosis after massive intestinal resection

J Pediatr Surg. 2006 Apr;41(4):713-8; discussion 713-8. doi: 10.1016/j.jpedsurg.2005.12.015.

Abstract

Background: We have previously established the significance of epidermal growth factor receptor (EGFR) activity and the cyclin-dependent kinase inhibitor p21waf1/cip1 (p21) for the adaptive response of the intestine to massive small bowel resection (SBR). In this study, we tested the role of the signal transducer and activator of transcription 1 (STAT-1) as this transcription factor is activated by the EGFR and known to induce p21 expression.

Methods: Control (n = 40; C57/Bl6) and STAT-1-null mice (n = 40) underwent 50% proximal SBR or sham operation. After 3 days, the remnant ileum was harvested and the villus and crypt morphology was measured along with changes in rates of enterocyte proliferation and apoptosis.

Results: The magnitude of resection-induced adaptation was greater in STAT-1-null animals as verified by taller villi and deeper crypts. The expected increase in enterocyte apoptosis did not occur after SBR in the background of STAT-1 deficiency. Western blotting revealed elevated expression of p21 protein in both STAT-1-null and controls after SBR.

Conclusion: Increased p21 expression after SBR in the absence of STAT-1 suggests an alternate mechanism for resection-induced regulation of p21. Enhanced adaptation in STAT-1-null animals suggests that this transcription factor serves an inhibitor to the process of adaptation, perhaps via regulation of enterocyte apoptosis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptation, Physiological*
  • Animals
  • Apoptosis*
  • Cyclin-Dependent Kinase Inhibitor p21 / physiology
  • Digestive System Surgical Procedures / methods
  • Intestine, Small / surgery*
  • Mice
  • STAT1 Transcription Factor / biosynthesis
  • STAT1 Transcription Factor / physiology*

Substances

  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • STAT1 Transcription Factor