Free Content The specific expression of Hypoxia Inducible Factor-1α in human gastric mucosa induced by nonsteroidal anti-inflammatory drugs

Authors: Ito, M.; Tanaka, S.1; Kim, S.2; Kuwai, T.2; Matsutani, N.2; Kamada, T.3; Kitadai, Y.2; Sumii, M.2; Yoshihara, M.4; Haruma, K.3; Chayama, K.2

Source: Alimentary Pharmacology & Therapeutics, Volume 18, Supplement 1, July 2003 , pp. 90-98(9)

Publisher: Wiley-Blackwell

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Abstract:

Summary Background

: Hypoxia is a cause of gastric mucosal damage induced by nonsteroidal anti-inflammatory drugs (NSAIDs). The expression of hypoxia inducible factor-1α (HIF-1α) reflects the status of tissue ischaemia. Aim

: To investigate the effect of NSAID administration on the expression of HIF-1α in human gastric mucosa. Methods

: We employed 71 patients including 14 with NSAID administration. The HIF-1α expression was estimated by immunohistochemistry using monoclonal antibody (H1α67) and raised antiserum (HI-3). Vascular endothelial growth factor expression was also examined by immunohistochemistry. HI-3 recognized hypoxia-induced protein in HeLa cells. Results

: In human gastric mucosa, HIF-1α was mainly expressed in the nuclei of the surface epithelial cells and in the neck zone both by use of HI-3 and of H1α67. The expression of vascular endothelial growth factor correlated well with that of HIF-1α. The level of HIF-1α in the surface epithelium was significantly higher in patients with administration of NSAIDs than those without NSAID use (P < 0.001) both in the gastric corpus and antrum. Helicobacter pylori infection did not affected the levels of HIF-1α. Long-term administration of rebamipide reduced the level of HIF-1α. Conclusion

: HIF-1α expression is a new biological marker of ischaemia especially in NSAID-related gastric lesions.

Document Type: Research article

DOI: http://dx.doi.org/10.1046/j.1365-2036.18.s1.10.x

Affiliations: 1: Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan; 2: Department of Medicine and Molecular Science, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan; 3: Division of Gastroenterology II, Department of Internal Medicine, Kawasaki Medical School, Kurashiki, Japan; 4: Health Service Center, Hiroshima University, Higashi-Hiroshima, Japan

Publication date: 2003-07-01

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