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Degradation of soluble VEGF receptor-1 by MMP-7 allows VEGF access to endothelial cells
| Content Provider | Scilit |
|---|---|
| Author | Ito, Ta-Kashi Ishii, Genichiro Saito, Seiji Yano, Keiichi Hoshino, Ayuko Suzuki, Tasuku Ochiai, Atsushi |
| Copyright Year | 2009 |
| Description | Vascular endothelial growth factor (VEGF) signaling in endothelial cells serves a critical role in physiologic and pathologic angiogenesis. Endothelial cells secrete soluble VEGF receptor-1 (sVEGFR-1/sFlt-1), an endogenous VEGF inhibitor that sequesters VEGF and blocks its access to VEGF receptors. This raises the question of how VEGF passes through this endogenous VEGF trap to reach its membrane receptors on endothelial cells, a step required for VEGF-driven angiogenesis. Here, we show that matrix metalloproteinase-7 (MMP-7) degrades human sVEGFR-1, which increases VEGF bioavailability around the endothelial cells. Using a tube formation assay, migration assay, and coimmunoprecipitation assay with human umbilical vein endothelial cells (HUVECs), we show that the degradation of sVEGFR-1 by MMP-7 liberates the VEGF165 isoform from sVEGFR-1. The presence of MMP-7 abrogates the inhibitory effect of sVEGFR-1 on VEGF-induced phosphorylation of VEGF receptor-2 on HUVECs. These data suggest that VEGF escapes the sequestration by endothelial sVEGFR-1 and promotes angiogenesis in the presence of MMP-7. |
| Related Links | http://www.bloodjournal.org/content/113/10/2363.full.pdf |
| Ending Page | 2369 |
| Page Count | 7 |
| Starting Page | 2363 |
| DOI | 10.1182/blood-2008-08-172742 |
| Journal | Blood |
| Issue Number | 10 |
| Volume Number | 113 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 2009-03-05 |
| Access Restriction | Open |
| Subject Keyword | Cell Biology Research and Experimental Medicine Endothelial Cell Journal: Blood (Vol- 114, Issue- 10) |
| Content Type | Text |
| Resource Type | Article |
