Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 50 (6), 943-7

Both Epidermal Growth Factor and Insulin-Like Growth Factor Receptors Are Dispensable for Structural Intestinal Adaptation

Affiliations

Both Epidermal Growth Factor and Insulin-Like Growth Factor Receptors Are Dispensable for Structural Intestinal Adaptation

Raphael C Sun et al. J Pediatr Surg.

Abstract

Purpose: Intestinal adaptation structurally represents increases in crypt depth and villus height in response to small bowel resection (SBR). Previously, we found that neither epidermal growth factor receptor (EGFR) nor insulin-like growth factor 1 receptor (IGF1R) function was individually required for normal adaptation. In this study, we sought to determine the effect of disrupting both EGFR and IGF1R expression on resection-induced adaptation.

Methods: Intestinal-specific EGFR and IGF1R double knockout mice (EGFR/IGF1R-IKO) (n=6) and wild-type (WT) control mice (n=7) underwent 50% proximal SBR. On postoperative day (POD) 7, structural adaptation was scored by measuring crypt depth and villus height. Rates of crypt cell proliferation, apoptosis, and submucosal capillary density were also compared.

Results: After 50% SBR, normal adaptation occurred in both WT and EGFR/IGF1R-IKO. Rates of proliferation and apoptosis were no different between the two groups. The angiogenic response was less in the EGFR/IGF1R-IKO compared to WT mice.

Conclusion: Disrupted expression of EGFR and IGF1R in the intestinal epithelial cells does not affect resection-induced structural adaptation but attenuates angiogenesis after SBR. These findings suggest that villus growth is driven by receptors and pathways that occur outside the epithelial cell component, while angiogenic responses may be influenced by epithelial-endothelial crosstalk.

Keywords: Epidermal growth factor receptor; Insulin-like growth factor 1 receptor; Intestinal adaptation; Short gut syndrome.

Conflict of interest statement

Disclosures: the authors have no conflict of interest or financial disclosures

Figures

Figure 1
Figure 1
A) Western blot confirming deletion of EGFR and IGF1R protein expression in crypt enterocytes. Both EGFR and IGF1R expression were knocked out in the intestinal epithelium in adult mice (EGFR/IGF1R-IKO; n=6) following the injection of tamoxifen. Both the knockout mice and wild-type (n=7) controls were administered tamoxifen for three days prior to resection. Tubulin was used as loading control. Successful deletion of EGFR and IGF1R protein was confirmed with all Villin Cre-ER(+); EGFR (f/f), IGF1R (f/f) mice. B) Percentage increase in crypt depth and villus height for EGFR/IGF1R-IKO (n=6) and WT (n=7) mice after small bowel resection. There were no statistical differences in postoperative villus or crypt growth between groups.
Figure 1
Figure 1
A) Western blot confirming deletion of EGFR and IGF1R protein expression in crypt enterocytes. Both EGFR and IGF1R expression were knocked out in the intestinal epithelium in adult mice (EGFR/IGF1R-IKO; n=6) following the injection of tamoxifen. Both the knockout mice and wild-type (n=7) controls were administered tamoxifen for three days prior to resection. Tubulin was used as loading control. Successful deletion of EGFR and IGF1R protein was confirmed with all Villin Cre-ER(+); EGFR (f/f), IGF1R (f/f) mice. B) Percentage increase in crypt depth and villus height for EGFR/IGF1R-IKO (n=6) and WT (n=7) mice after small bowel resection. There were no statistical differences in postoperative villus or crypt growth between groups.
Figure 2
Figure 2
Rates of crypt cell proliferation at baseline and 7 days after 50% proximal small bowel resection (SBR) in EGFR/IGF1R-IKO (n=6) and wild-type (WT; n=7) littermates. P-histone 3 immunostaining was performed on tissue sections and positively stained cells were counted in each crypt. A ratio was calculated as number of cells stained positive divided by total number of cells in the crypts. A minimum of 20 crypts were counted per mouse.
Figure 3
Figure 3
Angiogenesis at baseline and 7 days after 50% proximal small bowel resection (SBR) as measured by counting the number of cd31 positive-stained vessels per high power field. Ten high power fields were counted and averaged. Both EGFR/IGF1R-IKO (n=6) and wild-type (WT; n=7) mice showed an increase in cd31 positive stained vessels per high power field after SBR. However, EGFR/IGF1R-IKO mice had an impaired angiogenic response compared with the WT group (p-value<0.01).
Figure 4
Figure 4
Western blot demonstrates phosphorylation of ERK (Thr 202/Tyr 204) and AKT (Ser 473) pathways in both EGFR/IGF1R-IKO and WT mice in crypt enterocytes. Actin was used as a loading control.

Similar articles

See all similar articles

Cited by 3 articles

Publication types

Feedback