Smooth muscle overexpression of IGF-I induces a novel adaptive response to small bowel resection.
Prior studies of intestinal adaptation after massive small bowel resection (SBR) have focused on growth factors and their effects on amplification of the gut mucosa. Because adaptive changes have also been described in intestinal smooth muscle, we sought to determine the effect of targeted smooth muscle growth factor overexpression on resection-induced intestinal adaptation. Male transgenic mice with smooth muscle cell overexpression of insulin-like growth factor I (IGF-I) by virtue of an alpha-smooth muscle actin promoter were obtained. SMP8 IGF-I transgenic (IGF-I TG) and nontransgenic (NT) littermates underwent 50% proximal SBR or sham operation and were then killed after 3 or 28 days. NT mice showed the expected alterations in mucosal adaptive parameters after SBR, such as increased wet weight and villus height. The IGF-I TG mice had inherently taller villi, which did not increase significantly after SBR. In addition, IGF-I TG mice had a 50% postresection persistent increase in remnant intestinal length, which was associated with an early decline and later increase in relative mucosal surface area. These results indicate that growth factor overexpression within the muscularis layer of the bowel wall induces significant postresection adaptive intestinal lengthening and a unique mucosal response. IGF-I signaling within the muscle wall may play an important role in the pathogenesis of resection-induced adaptation.
Knott
Andrew W
AW
Division of Pediatric Surgery, Department of Surgery, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Mediicne, Cincinnati, Ohio 45229-3039, USA.
Juno
Russell J
RJ
Jarboe
Marcus D
MD
Profitt
Sherri A
SA
Erwin
Christopher R
CR
Smith
Eric P
EP
Fagin
James A
JA
Warner
Brad W
BW
D000222:Adaptation, Physiological / Q000235:genetics*; D000818:Animals; D002455:Cell Division; D017931:DNA Primers; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D020895:Enterocytes / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000235:genetics*; D007413:Intestinal Mucosa / Q000033:anatomy & histology / Q000378:metabolism; D007421:Intestine, Small / Q000033:anatomy & histology / Q000378:metabolism / Q000601:surgery*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009130:Muscle, Smooth / Q000033:anatomy & histology / Q000378:metabolism*; D009929:Organ Size / Q000502:physiology; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D018076:DNA, Complementary; D007334:Insulin-Like Growth Factor I