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  • Title: Heparin-binding EGF-like growth factor preserves crypt cell proliferation and decreases bacterial translocation after intestinal ischemia/reperfusion injury.
    Author: Xia G, Martin AE, Michalsky MP, Besner GE.
    Journal: J Pediatr Surg; 2002 Jul; 37(7):1081-7; discussion 1081-7. PubMed ID: 12077776.
    Abstract:
    BACKGROUND/PURPOSE: Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF), a known mitogenic, chemotactic, and cytoprotective growth factor for epithelial cells, was examined to see whether it could protect intestinal barrier function and decrease bacterial translocation (BT) after ischemia/reperfusion (I/R) injury. METHODS: In vitro, tight junctional integrity of intestinal epithelial cells (IEC-6) cells was evaluated by measuring transepithelial electric resistance (TEER), and monolayer permeability was evaluated by translocation of Escherichia coli C25. In vivo, crypt cell proliferation was assessed by 5-bromodeoxyuridine incorporation with calculation of a proliferative index (PI), and BT was evaluated by culture of mesenteric lymph nodes. RESULTS: In vitro, anoxia damaged tight junctional integrity and increased permeability of IEC-6 cell monolayers, events that were reversed completely by treatment of the cells with HB-EGF. Twenty-four hours after I/R injury in vivo, crypt cell proliferation index (PI) decreased significantly from 35.6 +/- 4.5 to 17.8 +/- 3.4. Administration of HB-EGF preserved crypt cell activity with PI of 34.9 +/- 4.1, similar to that of normal ileum. None of the normal or sham-operated animals showed BT, whereas BT occurred in 87.5% of I/R-injured rats. In animals exposed to I/R but treated with HB-EGF, BT was decreased significantly to 12.5%. CONCLUSION: HB-EGF preserves proliferation of crypt cells, maintains integrity of epithelial cells, and subsequently decreases enteric BT after I/R injury.
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