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


CONCLUSIONS
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.
Stehr
Wolfgang
W
Division 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.
Bernal
Nicole P
NP
Bernabe
Kathryn Q
KQ
Erwin
Christopher R
CR
Warner
Brad W
BW
D000222:Adaptation, Physiological; D000818:Animals; D017209:Apoptosis; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000502:physiology; D013505:Digestive System Surgical Procedures / Q000379:methods; D007421:Intestine, Small / Q000601:surgery*; D051379:Mice; D050794:STAT1 Transcription Factor / Q000096:biosynthesis / Q000502:physiology*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050794:STAT1 Transcription Factor