MicroRNA-24-3p Targets Notch and Other Vascular Morphogens to Regulate Post-ischemic Microvascular Responses in Limb Muscles

International Journal of Molecular Sciences
Micol MarchettiCostanza Emanueli

Abstract

MicroRNAs (miRs) regulate complex processes, including angiogenesis, by targeting multiple mRNAs. miR-24-3p-3p directly represses eNOS, GATA2, and PAK4 in endothelial cells (ECs), thus inhibiting angiogenesis during development and in the infarcted heart. miR-24-3p is widely expressed in cardiovascular cells, suggesting that it could additionally regulate angiogenesis by acting on vascular mural cells. Here, we have investigated: 1) new miR-24-3p targets; 2) the expression and the function of miR-24-3p in human vascular ECs; 3) the impact of miR-24-3p inhibition in the angiogenesis reparative response to limb ischemia in mice. Using bioinformatics target prediction platforms and 3'-UTR luciferase assays, we newly identified Notch1 and its Delta-like ligand 1 (Dll1) to be directly targeted by miR-24-3p. miR-24-3p was expressed in human ECs and pericytes cultured under normal conditions. Exposure to hypoxia increased miR-24-3p in ECs but not in pericytes. Transfection with a miR-24-3p precursor (pre-miR-24-3p) increased miR-24-3p expression in ECs, reducing the cell survival, proliferation, and angiogenic capacity. Opposite effects were caused by miR-24-3p inhibition. The anti-angiogenic action of miR-24-3p overexpression could b...Continue Reading

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Citations

Dec 23, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Gang WangMao Luo
Jan 28, 2021·Immunological Investigations·Yeping LuoZuocheng Yang
Feb 10, 2021·Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus·Gabriel Gil-GómezManuel Pera

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Methods Mentioned

BETA
transfection
flow cytometry
amputation
ubiquitination
PCR
Assay
reverse transcription PCR
confocal microscopy

Software Mentioned

miRanda
PicTar
Diana
rna22
TargetScan
Volocity
mirWalk
miRbase
ARRIVE
ImageJ

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