Increased indomethacin-induced gastric ulcers in TFF2-deficient mice. (a) Histological sections of indomethacin-induced ulceration in TFF2-deficient mice. Superficial erosion with significant epithelial disruption and minimal inflammatory infiltrate (top). Deeper ulceration extending to the muscularis mucosae with moderate numbers of inflammatory cells (middle). Broad-based gastric ulceration with large numbers of inflammatory cells (bottom). (b) Dose response. Gastric mucosal lesions were assessed following administration of indomethacin (20 and 40 mg/kg) for 12 hours and 1 hour following bethanechol (2.5 mg/kg). There was a significant difference (* P < 0.03) with the 40 mg/kg dose, while there was not a clearly significant difference (P < 0.14) with the 20 mg/kg dose. (c) Time-dependent response with indomethacin 40 mg/kg. Gastric mucosal lesions were assessed 12 to 24 hours following administration of indomethacin (40 mg/kg) and 1 hour following administration of bethanechol (2.5 mg/kg). Most gastric lesions were linear, thus data is expressed as mean of ulcers seen per horizontal stomach section (six horizontal sections per stomach). The differences at both 12 hours (**P < 0.04) and 24 hours (***P < 0.02) were statistically significant. (d) Gastric indomethacin-induced ulcer damage and inflammation score. Ulcer score after administration of indomethacin (20 mg/kg) for 24 hours. Significant increase in ulcer damage score (****P < 0.03) seen in TFF2-deficient mice after administration of indomethacin 20 mg/kg for 24 hours compared with wild-type mice. No significant difference was seen in the inflammatory score between TFF2-deficient mice or wild-type mice.