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.
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.
Wolfgang
W
Stehr
Nicole P
NP
Bernal
Kathryn Q
KQ
Bernabe
Christopher R
CR
Erwin
Brad W
BW
Warner
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