| First Author | Hou Y | Year | 2007 |
| Journal | Cardiovasc Res | Volume | 75 |
| Issue | 1 | Pages | 186-94 |
| PubMed ID | 17382917 | Mgi Jnum | J:124454 |
| Mgi Id | MGI:3721729 | Doi | 10.1016/j.cardiores.2007.02.033 |
| Citation | Hou Y, et al. (2007) c-Myc is essential for urokinase plasminogen activator expression on hypoxia-induced vascular smooth muscle cells. Cardiovasc Res 75(1):186-94 |
| abstractText | OBJECTIVES: The purpose of this study was to investigate whether c-Myc regulates expression of urokinase plasminogen activator (uPA) on hypoxia-induced vascular smooth muscle cells (VSMCs). METHODS: VSMCs were isolated from thoracic aorta of wild-type (WT), tissue plasminogen activator (tPA) and uPA-deficient mice. Gene and protein expression levels were examined by reverse-transcription PCR and Western blotting, respectively. c-Myc and uPA transcriptional activity were determined by luciferase analysis. Zymography analysis was used to test the activity of matrix metalloproteinases (MMPs), tPA, and uPA. RESULTS: Hypoxia significantly promoted WT and tPA-/- VSMC migration and invasion. However, uPA-/- severely decreased hypoxia-induced VSMC migration and invasion. Hypoxia increased uPA and MMP-2 activity, while uPA-/- decreased hypoxia-induced MMP-2 activity. c-Myc expression and transcriptional activity were increased in response to hypoxia, and silenced c-Myc abolished hypoxia-induced uPA and MMP-2 activity. In addition, hypoxia-induced Bcl2 expression and Bcl2 binding to c-Myc led to enhanced c-Myc-mediated uPA and MMP-2 activity in response to hypoxia. CONCLUSIONS: The results show that c-Myc was essential for hypoxia-induced uPA expression and activity, resulting in VSMC migration and invasion. In addition, Bcl2 enhanced the c-Myc-mediated uPA/MMP-2 pathway. |
