Taylor Janice A, Bernabe Kathryn Q, Guo Jun, Warner Brad W
Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH 45229-3039, USA.
J Pediatr Surg. 2007 Jun;42(6):981-6. doi: 10.1016/j.jpedsurg.2007.01.032.
Epidermal growth factor receptor (EGFR) stimulation enhances intestinal adaptation after massive small bowel resection (SBR), measured by taller villi, deeper crypts, and augmented enterocyte proliferation. Min mice with constitutively active beta-catenin signaling demonstrate enhanced villus growth after SBR, suggesting a role for the Wnt pathway during adaptation. Because there is crosstalk between EGFR signaling and the Wnt pathway, we hypothesized that beta-catenin is modulated by EGFR-induced enterocyte proliferation.
Rat intestinal epithelial cells were stimulated with EGF and cytoplasmic to nuclear trafficking of beta-catenin was measured. Beta-catenin-directed transcription was also tested via transfection with a TOP/FOP luciferase reporter. Downstream transcriptional target expression was measured in murine intestine after SBR.
Epidermal growth factor-treated rat intestinal epithelial cells exhibited increased proliferation compared to serum-deficient cells in the face of no detectable accumulation of nuclear beta-catenin. The luciferase assay results showed minimal transcription activity in response to EGF. In vivo experiments revealed no significant difference in expression of beta-catenin targeted genes in crypt enterocytes after SBR.
The mechanism for EGFR-induced proliferation of enterocytes does not appear to involve a transcriptional role for beta-catenin. The effects of EGFR signaling on beta-catenin-mediated cell adhesion remain to be investigated.
表皮生长因子受体（EGFR）刺激可增强大规模小肠切除术后的肠道适应性，这可通过更高的绒毛、更深的隐窝以及增强的肠上皮细胞增殖来衡量。具有组成型活性β-连环蛋白信号传导的Min小鼠在小肠切除术后表现出绒毛生长增强，提示Wnt通路在适应性过程中发挥作用。由于EGFR信号传导与Wnt通路之间存在相互作用，我们推测β-连环蛋白受EGFR诱导的肠上皮细胞增殖调节。
用表皮生长因子刺激大鼠肠上皮细胞，并检测β-连环蛋白从细胞质到细胞核的转运。还通过用TOP/FOP荧光素酶报告基因转染来测试β-连环蛋白指导的转录。在小肠切除术后的小鼠肠道中测量下游转录靶标的表达。
与血清缺乏的细胞相比，表皮生长因子处理的大鼠肠上皮细胞增殖增加，但未检测到核β-连环蛋白的积累。荧光素酶测定结果显示，对表皮生长因子的反应转录活性最低。体内实验显示，小肠切除术后隐窝肠上皮细胞中β-连环蛋白靶向基因的表达无显著差异。
EGFR诱导肠上皮细胞增殖的机制似乎不涉及β-连环蛋白的转录作用。EGFR信号传导对β-连环蛋白介导的细胞黏附的影响仍有待研究。
