Reference - Detail
| RRC ID | 41468 |
|---|---|
| Author | Pai R, Szabo IL, Giap AQ, Kawanaka H, Tarnawski AS. |
| Title | Nonsteroidal anti-inflammatory drugs inhibit re-epithelialization of wounded gastric monolayers by interfering with actin, Src, FAK, and tensin signaling. |
| Journal | Life Sci |
| Abstract |
Re-epithelialization is essential for gastrointestinal ulcer and cutaneous wound healing. It requires epithelial cell migration and proliferation, processes that are stimulated by epidermal growth factor (EGF), and dependent on the cell cytoskeleton. Activation of Src and focal adhesion kinase (FAK) has been implicated in EGF-stimulated cell migration. Nonsteroidal anti-inflammatory drugs (NSAIDs) (both nonselective and Cox2-selective) interfere with ulcer healing and re-epithelialization in vitro and in vivo, but the cellular targets and mechanisms remain unexplored forming the basis of this study. Using a wounded gastric epithelial cell monolayer model, we demonstrated that NSAIDs reduce both basal and epidermal growth factor (EGF)-induced re-epithelialization, and that this action involves disruption of actin stress fiber formation, reduced c-Src activity, decreased phosphorylation of focal adhesion kinase (FAK), tensin and their cellular re-distribution. There was a strong correlation between NSAIDs-mediated inhibitory effect on re-epithelialization and loss of stress fibers and reduced tensin signal. Furthermore, NSAIDs significantly reduced EGF-stimulated c-Src association with FAK. These findings suggest that NSAIDs can directly affect the cell cytoskeleton and signaling pathways essential for re-epithelialization. |
| Volume | 69(25-26) |
| Pages | 3055-71 |
| Published | 2001-11-9 |
| DOI | 10.1016/s0024-3205(01)01412-6 |
| PII | S0024-3205(01)01412-6 |
| PMID | 11758831 |
| MeSH | Actins / metabolism Animals Anti-Inflammatory Agents, Non-Steroidal / pharmacology* Cell Line Cell Movement / drug effects Cyclooxygenase Inhibitors / pharmacology* Cytoskeleton / drug effects Dose-Response Relationship, Drug Drug Interactions Epidermal Growth Factor / pharmacology Focal Adhesion Kinase 1 Focal Adhesion Protein-Tyrosine Kinases Gastric Mucosa / drug effects* Gastric Mucosa / metabolism Gastric Mucosa / pathology Indomethacin / pharmacology Microfilament Proteins / metabolism Nitrobenzenes / pharmacology Protein-Tyrosine Kinases / metabolism Rats Signal Transduction / drug effects* Sulfonamides / pharmacology Tensins Wound Healing / drug effects* src-Family Kinases / metabolism |
| IF | 3.647 |
| Times Cited | 40 |
| WOS Category | PHARMACOLOGY & PHARMACY MEDICINE, RESEARCH & EXPERIMENTAL |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | RGM1(RCB0876) |