Interaction of hepatocyte growth factor and non-steroidal anti-inflammatory drugs during gastric epithelial wound healing.
OBJECTIVE
Expression of the hepatocyte growth factor (HGF) and cyclooxygenase-2 (COX-2) is upregulated at the margins of healing gastric ulcers. We investigated in vitro the interference of HGF, the selective COX-2 inhibitor NS-398 and the nonselective COX inhibitor indomethacin with gastric epithelial wound healing and actin microfilament (actin-MF) formation.


METHODS
Standardized gastric epithelial wounds, created in confluent RGM1 rat cell monolayers were treated with: HGF (10 ng/ml), NS-398 (1-100 microM) or indomethacin (0.01- 0.5 mM). The areas of re-epithelialization and cell proliferation were measured 24 h after wounding. Actin-MFs were labeled with fluorescein-conjugated phalloidin and their distribution was examined using a Nikon epifluorescence microscope.


RESULTS
HGF caused a significant increase in gastric monolayer wound re-epithelialization and this was not affected by mitomycin C. Both indomethacin and NS-398 inhibited HGF-stimulated re-epithelialization, but the basal wound re-epithelialization rate and cell proliferation was only significantly inhibited by indomethacin. HGF triggered actin stress fiber formation which was inhibited by both indomethacin and NS-398, but only indomethacin interfered with actin-MF formation at the baseline condition.


CONCLUSIONS
HGF significantly increased gastric wound re-epithelialization by activating cell migration which may be mediated by the COX-2 pathway.
Netzer
Peter
P
VA Medical Center Long Beach, California, USA. peter.netzer@insel.ch
Halter
Fred
F
Ma
Thomas Y
TY
Hoa
Neil
N
Nguyen
Nathan
N
Nakamura
Toshikazu
T
Tarnawski
Andrzej S
AS
D000199:Actins / Q000187:drug effects*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005753:Gastric Mucosa / Q000187:drug effects*; D006133:Growth Substances / Q000494:pharmacology*; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology*; D023421:Models, Animal; D009578:Nitrobenzenes / Q000494:pharmacology*; D051381:Rats; D013276:Stomach Ulcer / Q000503:physiopathology; D013449:Sulfonamides / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*
D000199:Actins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D006133:Growth Substances; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D017228:Hepatocyte Growth Factor; D007213:Indomethacin