The specific expression of hypoxia inducible factor-1alpha in human gastric mucosa induced by nonsteroidal anti-inflammatory drugs.
BACKGROUND
Hypoxia is a cause of gastric mucosal damage induced by nonsteroidal anti-inflammatory drugs (NSAIDs). The expression of hypoxia inducible factor-1alpha (HIF-1alpha) reflects the status of tissue ischaemia.


OBJECTIVE
To investigate the effect of NSAID administration on the expression of HIF-1alpha in human gastric mucosa.


METHODS
We employed 71 patients including 14 with NSAID administration. The HIF-1alpha expression was estimated by immunohistochemistry using monoclonal antibody (H1alpha67) 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-1alpha was mainly expressed in the nuclei of the surface epithelial cells and in the neck zone both by use of HI-3 and of H1alpha67. The expression of vascular endothelial growth factor correlated well with that of HIF-1alpha. The level of HIF-1alpha 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-1alpha. Long-term administration of rebamipide reduced the level of HIF-1alpha.


CONCLUSIONS
HIF-1alpha expression is a new biological marker of ischaemia especially in NSAID-related gastric lesions.
Ito
M
M
Department of Medicine and Molecular Science, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan. maito@hiroshima-u.ac.jp
Tanaka
S
S
Kim
S
S
Kuwai
T
T
Matsutani
N
N
Kamada
T
T
Kitadai
Y
Y
Sumii
M
M
Yoshihara
M
M
Haruma
K
K
Chayama
K
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015363:Quinolones / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D015363:Quinolones; D014157:Transcription Factors; C052785:rebamipide; D000409:Alanine