The adaptive intestinal response to massive enterectomy is preserved in c-SRC-deficient mice.
OBJECTIVE
The Src family of protein tyrosine kinases has been implicated in the downstream mitogenic signaling of several ligands including epidermal growth factor (EGF). Because EGF likely plays a role in adaptation after massive small bowel resection (SBR), we tested the hypothesis that c-src is required for this important response.


METHODS
A 50% proximal SBR or sham operation (bowel transection or reanastomosis alone) was performed on c-src-deficient (n = 14) or wild-type (C57bl/6) mice (n = 20). The ileum was harvested on postoperative day 3 and adaptive parameters determined as changes in ileal wet weight, protein and DNA content, proliferation index, villus height, and crypt depth. Comparisons were done using analysis of variance (ANOVA), and a Pvalue less than .05 was considered significant. Values are presented as mean +/- SEM.


RESULTS
The activity of c-src was increased in the ileum of wild-type mice after SBR but remained unchanged in c-src-deficient mice. Despite this lack of increase, adaptation occurred after SBR in the c-src-deficient mice as demonstrated by increased ileal wet weight, protein and DNA content, proliferation index, villus height, and crypt depth similar to wild-type mice.


CONCLUSIONS
The adaptive response of the intestine to massive SBR is preserved despite reduced activity of the c-src protein. The mitogenic signaling that characterizes intestinal adaptation and is associated with receptor activation by EGF or other growth factors probably occurs by mechanisms independent of c-src protein tyrosine kinase.
Falcone
R A
RA
Children's Hospital Medical Center, and the Department of Surgery, University of Cincinnati College of Medicine, OH 45229-3039, USA.
Shin
C E
CE
Erwin
C R
CR
Warner
B W
BW
D000222:Adaptation, Physiological / Q000235:genetics; D000818:Animals; D013505:Digestive System Surgical Procedures; D015870:Gene Expression; D007421:Intestine, Small / Q000378:metabolism* / Q000601:surgery*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000096:biosynthesis* / Q000235:genetics
D011505:Protein-Tyrosine Kinases; D016392:Proto-Oncogene Proteins pp60(c-src)