Thrombin Induces EGF Receptor Expression and Cell Proliferation via a PKC(δ)/c-Src-Dependent Pathway in Vascular Smooth Muscle Cells
| Autor: | Cheng-Ying Wu, Wei-Hsuan Tung, Hsi-Lung Hsieh, Chuen-Mao Yang, Hui-Hsin Wang, Tze-Shyuan Wang, Chih-Chung Lin |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
MAPK/ERK pathway
medicine.medical_specialty Receptor expression Myocytes Smooth Muscle GTP-Binding Protein alpha Subunits Gi-Go Biology Muscle Smooth Vascular CSK Tyrosine-Protein Kinase Rats Sprague-Dawley Small hairpin RNA Phosphatidylinositol 3-Kinases Transactivation Internal medicine medicine Animals Phosphorylation Extracellular Signal-Regulated MAP Kinases Protein kinase B Cells Cultured Protein kinase C PI3K/AKT/mTOR pathway Cell Proliferation NF-kappa B Thrombin DNA Protein-Tyrosine Kinases Rats Cell biology ErbB Receptors Transcription Factor AP-1 Protein Kinase C-delta src-Family Kinases Endocrinology GTP-Binding Protein alpha Subunits Gq-G11 Signal transduction Cardiology and Cardiovascular Medicine Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 29:1594-1601 |
| ISSN: | 1524-4636 1079-5642 |
| DOI: | 10.1161/atvbaha.109.185801 |
| Popis: | Objection— Thrombin upregulates expression of several proteins in vascular smooth muscle cells (VSMCs) which may contribute to atherosclerosis. Here, we investigated the mechanisms underlying thrombin-induced EGF receptor (EGFR) expression and its effect on VSMCs. Methods and Results— Normal rat VSMCs were used. First, Western blotting and RT-PCR analyses showed that thrombin induces the expression of EGFR at transcription and translation levels in VSMCs. Second, pharmacological inhibitors, dominant negative mutants, and short hairpin RNA interference (shRNA) technology enabled us to demonstrate that thrombin-induced EGFR expression is mediated through PKC(δ)/c-Src-dependent transactivation of EGFR linking to PI3K/Akt and ERK1/2. We further investigated whether the transcription factors AP-1 and NF-κB are involved in this response by a promoter assay. Finally, data obtained by using EGFR shRNA technology and XTT assay demonstrated that thrombin-enhanced VSMC proliferation was mediated through upregulation of EGFR. Conclusions— Our results demonstrate that thrombin-enhanced VSMC proliferation was mediated through upregulation of EGFR via a PKC(δ)/c-Src-dependent transactivation of EGFR, PI3K-Akt, and ERK, and AP-1/NF-κB pathway. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|