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

Digestive Diseases and Sciences volume 58, pages 1198–1206 (2013)Cite this article

Abstract

Background and Aims

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.

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Abbreviations

Cygb:

Cytoglobin

NO:

Nitric oxide

HRE:

Hypoxia response element

HIF:

Hypoxia-inducible factor

VEGF:

Vascular endothelial growth factor

RT-PCR:

Reverse transcription-polymerase chain reaction

α-SMA:

α-smooth muscle actin

vWF:

von Willebrand factor

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Author information

Affiliations

  1. Department of Gastroenterology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan

    Fumio Tanaka, Kazunari Tominaga, Mitsue Sogawa, Hirokazu Yamagami, Tetsuya Tanigawa, Masatsugu Shiba, Kenji Watanabe, Toshio Watanabe, Yasuhiro Fujiwara & Tetsuo Arakawa

  2. Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan

    Norifumi Kawada

  3. Department of Gastroenterology, Osaka City General Hospital, Osaka, Japan

    Eiji Sasaki

  4. PhoenixBio Co, Ltd, Hiroshima, Japan

    Katsutoshi Yoshizato

Authors
  1. Fumio Tanaka
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  2. Kazunari Tominaga
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  3. Eiji Sasaki
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  4. Mitsue Sogawa
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  5. Hirokazu Yamagami
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  6. Tetsuya Tanigawa
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  7. Masatsugu Shiba
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  8. Kenji Watanabe
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  9. Toshio Watanabe
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  10. Yasuhiro Fujiwara
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  11. Norifumi Kawada
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  12. Katsutoshi Yoshizato
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  13. Tetsuo Arakawa
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Corresponding author

Correspondence to Kazunari Tominaga.

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Tanaka, F., Tominaga, K., Sasaki, E. et al. Cytoglobin May Be Involved in the Healing Process of Gastric Mucosal Injuries in the Late Phase Without Angiogenesis. Dig Dis Sci 58, 1198–1206 (2013). https://doi.org/10.1007/s10620-012-2514-8

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  • DOI: https://doi.org/10.1007/s10620-012-2514-8

Keywords

  • Stomach ulcer
  • Hypoxia
  • Angiogenesis
  • Mesenchyme
  • Fibroblast