Effect of growth factors on epithelial restitution of human colonic mucosa in vitro

Background: Epithelial restitution enables resurfacing of epithelial discontinuities by enterocyte migration. This study investigated the effect of basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF-1), and epidermal growth factor (EGF) on restitution of human colonic mucosa in vitro. Methods: After base-line incubation human colonic mucosal strips, mounted in Ussing chambers, were luminally exposed to 0.5 mM sodium deoxycholate (NaDOC) for 10 min. Thereafter tissues were incubated with buffer alone or luminal buffer containing various concentrations of bFGF, IGF-1, and EGF for 3 h. Resistance (R) was calculated from potential difference (PD) and shea-circuit current (Isc). All tissues were processed for light microscopy. Extent of damage was measured by morphometry. Results: Luminal 0.5 mM NaDOC for 10 min caused R to drop by 43% (n = 4; P < 0.05). Compared with controls 50 ng/ml EGF induced an approximately 30% R increase until the end of the experiments (P < 0.05, n = 4, paired). Ten minutes after injury 50.2 +/- 4% of the mucosa was damaged (n = 6), and after 3 h damage was significantly reduced by EGF (17.2 +/- 3% versus 31.7 +/- 4%, 50 ng/ml EGF versus controls) (P < 0.05, n = 6 per group). Histology showed that EGF stimulated enterocyte migration over the basal lamina. Various doses of bFGF and IGF-1 did not impair restitution when compared with controls. Conclusion: In contrast to bFGF and IGF-1, EGF was shown to promote epithelial restitution of human colonic mucosa in vitro.