Interaction of hepatocyte growth factor and non-steroidal anti-inflammatory drugs during gastric epithelial wound healing

Peter Netzer, Fred Halter, Thomas Ma, Neil Hoa, Nathan Nguyen, Toshikazu Nakamura, Andrzej S. Tarnawski

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background/Aims: 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 μM) 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-epi-thelialization, 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.

Original languageEnglish (US)
Pages (from-to)118-128
Number of pages11
JournalDigestion
Volume67
Issue number3
DOIs
StatePublished - Jul 21 2003

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Re-Epithelialization
Gastrointestinal Agents
Hepatocyte Growth Factor
Wound Healing
Indomethacin
Anti-Inflammatory Agents
Stomach
Cyclooxygenase 2
Actin Cytoskeleton
Actins
Cell Proliferation
Phalloidine
Stress Fibers
Cyclooxygenase 2 Inhibitors
Mitomycin
Stomach Ulcer
Fluorescein
Cell Movement
N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Gastroenterology

Cite this

Netzer, Peter ; Halter, Fred ; Ma, Thomas ; Hoa, Neil ; Nguyen, Nathan ; Nakamura, Toshikazu ; Tarnawski, Andrzej S. / Interaction of hepatocyte growth factor and non-steroidal anti-inflammatory drugs during gastric epithelial wound healing. In: Digestion. 2003 ; Vol. 67, No. 3. pp. 118-128.
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abstract = "Background/Aims: 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 μM) 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-epi-thelialization, 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.",
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Interaction of hepatocyte growth factor and non-steroidal anti-inflammatory drugs during gastric epithelial wound healing. / Netzer, Peter; Halter, Fred; Ma, Thomas; Hoa, Neil; Nguyen, Nathan; Nakamura, Toshikazu; Tarnawski, Andrzej S.

In: Digestion, Vol. 67, No. 3, 21.07.2003, p. 118-128.

Research output: Contribution to journalArticle

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T1 - Interaction of hepatocyte growth factor and non-steroidal anti-inflammatory drugs during gastric epithelial wound healing

AU - Netzer, Peter

AU - Halter, Fred

AU - Ma, Thomas

AU - Hoa, Neil

AU - Nguyen, Nathan

AU - Nakamura, Toshikazu

AU - Tarnawski, Andrzej S.

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N2 - Background/Aims: 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 μM) 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-epi-thelialization, 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.

AB - Background/Aims: 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 μM) 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-epi-thelialization, 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.

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