R A Falcone1, C E Shin, C R Erwin, B W Warner. 1. Children's Hospital Medical Center, and the Department of Surgery, University of Cincinnati College of Medicine, OH 45229-3039, USA.
Abstract
BACKGROUND/ PURPOSE: 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.
BACKGROUND/ PURPOSE: 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.