PRIMARY OBJECTIVE: Heparin-binding EGF-like growth factor (HB-EGF) protects the intestine from damage in animals. Future clinical trials of HB-EGF may involve administration of repeated doses of HB-EGF. Since HB-EGF activates EGF receptors which have been implicated in tumor development, we examined the effects of HB-EGF overexpression in the intestine. RESEARCH DESIGN: We generated transgenic (TG) mice in which the human HB-EGF gene is driven by the villin promoter to overexpress HB-EGF along the crypt-villous axis from the duodenum to the colon. RESULTS: HB-EGF TG mice have increased enterocyte proliferation balanced by increased enterocyte apoptosis. Despite prolonged overexpression of HB-EGF, no evidence of intestinal hyperplasia or tumor formation occurs. Although HB-EGF TG mice have no significant phenotypic alterations under basal conditions, they have increased resistance to intestinal injury. CONCLUSIONS: Prolonged intestinal HB-EGF overexpression results in no significant phenotypic alterations under basal conditions, but confers protection against intestinal injury.
PRIMARY OBJECTIVE:Heparin-binding EGF-like growth factor (HB-EGF) protects the intestine from damage in animals. Future clinical trials of HB-EGF may involve administration of repeated doses of HB-EGF. Since HB-EGF activates EGF receptors which have been implicated in tumor development, we examined the effects of HB-EGF overexpression in the intestine. RESEARCH DESIGN: We generated transgenic (TG) mice in which the humanHB-EGF gene is driven by the villin promoter to overexpress HB-EGF along the crypt-villous axis from the duodenum to the colon. RESULTS:HB-EGF TG mice have increased enterocyte proliferation balanced by increased enterocyte apoptosis. Despite prolonged overexpression of HB-EGF, no evidence of intestinal hyperplasia or tumor formation occurs. Although HB-EGF TG mice have no significant phenotypic alterations under basal conditions, they have increased resistance to intestinal injury. CONCLUSIONS: Prolonged intestinal HB-EGF overexpression results in no significant phenotypic alterations under basal conditions, but confers protection against intestinal injury.
Authors: Andrei Radulescu; Hong-Yi Zhang; Xiaoyi Yu; Jacob K Olson; Amanda K Darbyshire; Yan Chen; Gail E Besner Journal: J Pediatr Surg Date: 2010-10 Impact factor: 2.545
Authors: Iyore A O James; Chun-Liang Chen; Guangcun Huang; Hong-Yi Zhang; Markus Velten; Gail E Besner Journal: J Surg Res Date: 2010-04-24 Impact factor: 2.192
Authors: Hong-yi Zhang; Andrei Radulescu; Chun-liang Chen; Jacob K Olson; Amanda K Darbyshire; Gail E Besner Journal: Surgery Date: 2010-10-20 Impact factor: 3.982
Authors: Andrei Radulescu; Hong-Yi Zhang; Chun-Liang Chen; Yan Chen; Yu Zhou; Xiaoyi Yu; Iyore Otabor; Jacob K Olson; Gail E Besner Journal: J Surg Res Date: 2010-09-08 Impact factor: 2.192