4.7 Article

Lipoxin A4 stimulates endothelial miR-126-5p expression and its transfer via microvesicles

Journal

FASEB JOURNAL
Volume 31, Issue 5, Pages 1856-1866

Publisher

FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.201600952R

Keywords

proresolving mediators; vascular repair; microRNA; intercellular signaling; inflammation

Funding

  1. Italian Ministry of Education, University and Research [2010YK7Z5K_ 002]

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The proresolution lipid mediator lipoxin (LX) A(4) bestows protective bioactions on endothelial cells. We examined the impact of LXA(4) on transcellular endothelial signaling via microRNA(miR)-containing microvesicles. We report LXA(4) inhibition of MV release by TNF-alpha-treated HUVECs, associated with the down-regulation of 18 miR in endothelial microvesicles (EMVs) and the up-regulation of miR-126-5p, both in HUVECs and in EMVs. LXA(4) upregulated miR-126-5p by similar to 5-fold in HUVECs and promoted a release of microvesicles (LXA(4)-EMVs) that enhanced miR-126-5p by similar to 7-fold in recipient HUVECs. In these cells, LXA(4)-EMVs abrogated the up-regulation of VCAM-1, induced in recipient HUVECs by EMVs released by untreated or TNF-alpha-treatedHUVECs. LXA(4)-EMVs also reduced by similar to 40% the expression of SPRED1, which we validated as an miR-126-5p target, whereas they stimulated monolayer repair in an in vitro wound assay. This effect was lost when the EMVs were depleted of miR-126-5p. These results provide evidence that changes in miR expression and microvesicle packaging and transfer represent a mechanism of action of LXA(4), which may be relevant in vascular biology and inflammation.-Codagnone, M., Recchiuti, A., Lanuti, P., Pierdomenico, A. M., Cianci, E., Patruno, S., Mari, V. C., Simiele, F., Di Tomo, P., Pandolfi, A., Romano, M. Lipoxin A(4) stimulates endothelial miR-126-5p expression and its transfer via microvesicles.

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