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The specific expression of Hypoxia Inducible Factor‐1α in human gastric mucosa induced by nonsteroidal anti‐inflammatory drugs
Author(s) -
Ito M.,
Tanaka S.,
Kim S.,
Kuwai T.,
Matsutani N.,
Kamada T.,
Kitadai Y.,
Sumii M.,
Yoshihara M.,
Haruma K.,
Chayama K.
Publication year - 2003
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1046/j.1365-2036.18.s1.10.x
Subject(s) - medicine , immunohistochemistry , gastric mucosa , hypoxia (environmental) , helicobacter pylori , hypoxia inducible factors , vascular endothelial growth factor , antibody , pathology , stomach , immunology , biology , vegf receptors , chemistry , biochemistry , organic chemistry , oxygen , gene
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.