title: Cytoglobin may be involved in the healing process of gastric mucosal injuries in the late phase without angiogenesis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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)-1α was evaluated by western blotting. We measured vascular endothelial growth factor (VEGF) mRNA by RT-PCR and examined localization of Cygb by immunofluorescence.
  
  
  RESULTS
  In indomethacin-induced injury, Cygb protein was significantly increased at 24 h. In ulcerated tissues, HIF-1α protein was significantly increased on days 7 and 11 (1.83 ± 0.11 and 2.12 ± 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 ± 0.13 and 1.60 ± 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-1α were abundantly colocalized at the ulcer margin before angiogenesis development. However, faint localization was observed with angiogenesis.
  
  
  CONCLUSIONS
  Cygb may be involved in the healing process of gastric mucosal injuries in the late phase without angiogenesis.
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Tanaka
authors.forename: Kazunari
authors.initials: K
authors.lastname: Tominaga
authors.forename: Eiji
authors.initials: E
authors.lastname: Sasaki
authors.forename: Mitsue
authors.initials: M
authors.lastname: Sogawa
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Yamagami
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tanigawa
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Shiba
authors.forename: Kenji
authors.initials: K
authors.lastname: Watanabe
authors.forename: Toshio
authors.initials: T
authors.lastname: Watanabe
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Norifumi
authors.initials: N
authors.lastname: Kawada
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Yoshizato
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Arakawa
mesh_terms: D000818:Animals; D000078842:Cytoglobin; D005753:Gastric Mucosa / Q000293:injuries* / Q000378:metabolism; D005914:Globins / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008297:Male; D018919:Neovascularization, Physiologic; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing
chemical_list: C000627268:Cygb protein, rat; D000078842:Cytoglobin; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D005914:Globins