Transforming growth factor–β1 induces apoptosis in vascular endothelial cells by activation of mitogen-activated protein kinase
| Autor: | Paolo Mignatti, Jee Hyun Kim, Eugene A. Grossi, Aubrey C. Galloway, Graziano Seghezzi, Giulia Stellari, Kevin M Hyman, Giuseppe Pintucci |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
MAPK/ERK pathway
medicine.medical_specialty MAP Kinase Signaling System Blotting Western Apoptosis Mitogen-activated protein kinase kinase p38 Mitogen-Activated Protein Kinases Transforming Growth Factor beta1 Transforming Growth Factor beta Internal medicine medicine Animals ASK1 Protein kinase A Cells Cultured biology Akt/PKB signaling pathway Cyclin-dependent kinase 2 JNK Mitogen-Activated Protein Kinases Cell biology Vascular endothelial growth factor A Endocrinology biology.protein Cattle Surgery Endothelium Vascular Mitogen-Activated Protein Kinases Signal transduction |
| Zdroj: | Surgery. 132:173-179 |
| ISSN: | 0039-6060 |
| DOI: | 10.1067/msy.2002.125304 |
| Popis: | Background. Vascular endothelial cell apoptosis is central in atherosclerosis and intimal hyperplasia. Transforming growth factor (TGF)-β1 induces endothelial cell apoptosis through unidentified mechanism(s). Although TGF-β1 signals through the Smad proteins, in some nonendothelial cell types it also activates the mitogen-activated protein kinase (MAPK) (extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 MAPK [p38MAPK]). p38MAPK relays apoptotic signals in several cell types. We hypothesized that TGF-β1 activates endothelial cell MAPKs and induces apoptosis through p38MAPK activation. Methods. Human umbilical vein or bovine capillary endothelial cells were incubated with TGF-β1 for 0.5 to 12 hours. MAPK activation was characterized by Western blotting with antibodies to phosphorylated extracellular signal-regulated kinase 1/2, p38MAPK, or c-Jun N-terminal kinases 1/2. To study apoptosis, extracts of cells incubated with TGF-β1 for 6 hours with or without MAPK inhibitors were characterized by Western blotting analysis of poly (ADP-Ribose) polymerase degradation. Results. TGF-β1 induced p38MAPK, extracellular signal-regulated kinase 1/2, and c-Jun N-terminal kinase 1/2 activation and increased apoptosis. Inhibition of p38MAPK significantly reduced TGF-β1-induced apoptosis. In contrast, inhibition of other signaling pathways was ineffective. Conclusions. TGF-β1 induces endothelial cell apoptosis through p38MAPK activation. Because TGF-β1 is upregulated in vascular remodeling, p38MAPK is a potential target to prevent endothelial cell apoptosis during this process. (Surgery 2002;132:173-9.) |
| Databáze: | OpenAIRE |
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