Exacerbation of indomethacin-induced small intestinal injuries in Reg I-knockout mice

Nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal injuries are serious clinical events and a successful therapeutic strategy is difficult. Regenerating gene (Reg) I protein functions as a regulator of cell proliferation and maintains intercellular integrity in the small intestine. The aim of this study was to evaluate the role of Reg I in NSAID-induced small intestinal injuries. First, to examine the effect of Reg I deficiency on such injuries, indomethacin, a widely used NSAID, was injected subcutaneously into 10-wk-old male Reg I-knockout (Reg I−/−) and wild-type (Reg I+/+) mice twice with an interval of 24 h, after which the mice were euthanized. Small intestinal injuries were assessed by gross findings, histopathology, and contents of IL-1β and MPO in the experimental tissues. Next, we investigated the therapeutic potential of Reg I in indomethacin-induced small intestinal injuries. Recombinant Reg I protein (rReg I) was administered to 10-wk-old male ICR mice, then indomethacin was...