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Arterioscler Thromb Vasc Biol. 2012 Mar;32(3):633-42. doi: 10.1161/ATVBAHA.111.243576. Epub 2012 Jan 5.

Mirtron microRNA-1236 inhibits VEGFR-3 signaling during inflammatory lymphangiogenesis.

Author information

1
Interdepartmental Program in Vascular Biology and Therapeutics, Department of Immunobiology, Yale University School of Medicine, 10 Amistad St., New Haven, CT 06520, USA.

Abstract

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.

PMID:
22223733
PMCID:
PMC3288963
DOI:
10.1161/ATVBAHA.111.243576
[Indexed for MEDLINE]
Free PMC Article

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