Cytoglobin May Be Involved in the Healing Process of Gastric Mucosal Injuries in the Late Phase Without Angiogenesis

Cytoglobin (Cygb) is the newest globin family and is upregulated during hypoxia to maintain the oxygen status. Herein, we investigated Cygb expression in both acute and chronic gastric mucosal injuries. Acute gastric mucosal injuries in rats were produced by oral administration of indomethacin, followed by sacrifice at 1, 3, 6, 24, and 48 h. Gastric ulcer was produced by acetic acid, followed by sacrifice on days 3, 7, 11, 18, and 25. Each protein expression of Cygb and hypoxia-inducible factor (HIF)-1 alpha was evaluated by western blotting. We measured vascular endothelial growth factor (VEGF) mRNA by RT-PCR and examined localization of Cygb by immunofluorescence. In indomethacin-induced injury, Cygb protein was significantly increased at 24 h. In ulcerated tissues, HIF-1 alpha protein was significantly increased on days 7 and 11 (1.83 +/- A 0.11 and 2.12 +/- A 0.19 folds, respectively, p < 0.05 and 0.01), which corresponded to the early healing phase. In contrast, Cygb protein was significantly increased on days 11 and 18 (1.87 +/- A 0.13 and 1.60 +/- A 0.06 folds, respectively, p < 0.05), which demonstrated late phase. Though these proteins peaked on day 11, VEGF mRNA was gradually increased from day 11 to 18. Cygb was expressed in fibroblasts and myofibroblasts in both acute and chronic models. Cygb and HIF-1 alpha were abundantly colocalized at the ulcer margin before angiogenesis development. However, faint localization was observed with angiogenesis. Cygb may be involved in the healing process of gastric mucosal injuries in the late phase without angiogenesis.