Keratinocyte growth factor pretreatment prevents radiation-induced intestinal damage in a mouse model

Abstract

Background. Radiation-induced gastrointestinal syndrome is usually severe in clinical practice. Keratinocyte growth factor (KGF) plays an important role in the intestinal mucosal growth and repair of intestinal injury. This study was to investigate the effects of KGF on radiation-induced intestinal damage, especially the barrier dysfunction, in a mouse model. Methods. Adult C57BL/6J mice were randomized into three groups: normal control, irradiation group, and KGF-treated group. Mice in the later two groups received irradiation with a dose of 6 Gy from Co-60 source. In the KGF-treated group, KGF was intraperitoneally given once daily (5 mg/kg/day) for 5 consecutive days before irradiation. Mice were killed at 3 days after irradiation and the small bowel was collected for histology. Epithelial cell proliferation was studied by immunohistochemistry for proliferating cell nuclear antigen. Claudin-1 and ZO-1 expressions were determined by western blot assay and immunohistochemistry. Epithelial barrier function was assessed with transepithelial resistance. Results. KGF significantly promoted the recovery of mucosa from radiation-induced injury demonstrated by mucosal histology, villus height, crypt depth, and crypt cell proliferation. KGF also improved the disrupted distribution of tight junction proteins and the epithelial barrier dysfunction after irradiation. Conclusion. KGF pretreatment could improve radiation-induced intestinal injury including the epithelial structure and function in a mouse model.