Mirtron MicroRNA-1236 Inhibits VEGFR-3 Signaling During Inflammatory Lymphangiogenesis
Objective—Vascular endothelial growth factor receptor(VEGFR)-3 is a critical regulator of developmental and adult vasculogenesis and lymphangiogenesis through its interactions with select members of the VEGF family. The goal of this study was to investigate how VEGFR-3 expression is regulated during inflammatory lymphangiogenesis.
Methods and Results—In this study, we present for the first time evidence that VEGFR-3 can be negatively regulated by a mirtron, hsa-miR–1236 (miR-1236), which is expressed in primary human lymphatic endothelial cells. In human lymphatic endothelial cells, miR-1236 is upregulated in response to IL-1β, a negative regulator of VEGFR-3. miR-1236 binds the 3′ untranslated region of Vegfr3, resulting in translational inhibition. Overexpression of miR-1236 significantly decreased expression of VEGFR-3, but not VEGFR-2, in human lymphatic endothelial cells. Compared to a control miR, overexpression of miR-1236 also led to decreased VEGFR-3 signaling. However, VEGFR-2–specific signaling was not affected. miR-1236 can attenuate human lymphatic endothelial cell migration and tube formation, as well as in vivo lymphangiogenesis.
Conclusion—Our data suggest that miR-1236 may function as a negative regulator of VEGFR-3 signaling during inflammatory lymphangiogenesis.
- Received September 10, 2011.
- Accepted December 14, 2011.
- © 2012 American Heart Association, Inc.