Gastric restitution is inhibited by dexamethasone, which is reversed by hepatocyte growth factor and rebamipide.
BACKGROUND
Glucocorticoids have been shown to induce peptic ulcers, especially when co-administered with NSAIDs. Hepatocyte growth factor (HGF) plays a role in gastric ulcer repair, facilitating the restitution of gastric mucosal epithelial cells. HGF expression is induced by PGs in gastric fibroblasts. We hypothesized that dexamethasone (DEX) may inhibit PG production and HGF expression, thus inhibiting HGF-induced gastric epithelial restitution.


OBJECTIVE
To investigate the effect of DEX on gastric restitution, using cultured gastric cells, the role of HGF in the restitution inhibited by DEX, and the effect of rebamipide on DEX- inhibited restitution.


METHODS
Human gastric fibroblasts were prepared from human stomach obtained at surgery; PGE2 and HGF is determined by ELISA; Restitution was assessed by the round wound restitution model, using coculture of gastric fibroblasts and epithelial cells; COX-2 and HGF mRNA were quantified by TaqMan RT-PCR system.


RESULTS
1. DEX inhibited HGF mRNA and COX-2 mRNA. Accordingly, it inhibited PGE2 and HGF release. 2. DEX inhibited the restitution of gastric cells. 3. The inhibition of restitution was reversed by HGF and rebamipide to the same extent. 4. Rebamipide induced PGE2 and HGF.


CONCLUSIONS
DEX inhibits restitution via HGF depletion, and rebamipide reverses the inhibited restitution by HGF induction.
Takahashi
M
M
Department of Gastroenterology and Hepatology, University Hospital at Koshigaya, Dokkyo University School of Medicine, Saitama, Japan. mtak@dokkyomed.ac.jp
Takada
H
H
Takagi
K
K
Kataoka
S
S
Soma
R
R
Kuwayama
H
H
D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D003907:Dexamethasone / Q000494:pharmacology*; D015232:Dinoprostone / Q000037:antagonists & inhibitors; D005347:Fibroblasts / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects*; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D015363:Quinolones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000897:Anti-Ulcer Agents; D007527:Isoenzymes; D008565:Membrane Proteins; D015363:Quinolones; D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor; D003907:Dexamethasone; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; C052785:rebamipide; D000409:Alanine