Related Experiment Video
Updated: Aug 9, 2026
Effects of Taste Signaling Protein Abolishment on Gut Inflammation in an Inflammatory Bowel Disease Mouse Model
Published on: November 9, 2018
Absent STAT-1 expression perturbs adaptation and apoptosis after massive intestinal resection
Wolfgang Stehr1, Nicole P Bernal, Kathryn Q Bernabe
1Division of Pediatric General and Thoracic Surgery, Department of Surgery, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229-3039, USA.
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.
Insights
Signal transducer and activator of transcription 1 (STAT-1) deficiency enhances intestinal adaptation after small bowel resection (SBR). STAT-1-null mice show greater villus height and crypt depth, suggesting STAT-1 inhibits adaptation.
Area of Science:
- Gastroenterology
- Molecular Biology
- Cellular Biology
Background:
- Epidermal growth factor receptor (EGFR) activity and p21waf1/cip1 (p21) are crucial for intestinal adaptation post-small bowel resection (SBR).
- Signal transducer and activator of transcription 1 (STAT-1) is activated by EGFR and induces p21 expression.
Purpose of the Study:
- To investigate the role of STAT-1 in the adaptive response of the intestine following SBR.
- To determine if STAT-1 influences p21 expression and enterocyte apoptosis after SBR.
Main Methods:
- Control and STAT-1-null mice underwent 50% proximal SBR or sham operation.
- Ileum was harvested 3 days post-surgery to assess villus and crypt morphology, enterocyte proliferation, and apoptosis.
Main Results:
- STAT-1-null mice exhibited enhanced intestinal adaptation with significantly taller villi and deeper crypts compared to controls.
- Enterocyte apoptosis did not increase after SBR in STAT-1-null mice.
- Elevated p21 protein expression was observed in both STAT-1-null and control mice post-SBR.
Conclusions:
- Absence of STAT-1 leads to increased p21 expression, indicating an alternative pathway for p21 regulation after SBR.
- STAT-1 appears to inhibit intestinal adaptation post-SBR, potentially by regulating enterocyte apoptosis.
