miR-24 targets SARS-CoV-2 co-factor Neuropilin-1 in human brain microvascular endothelial cells: Insights for COVID-19 neurological manifestations

Abstract Neuropilin-1 is a transmembrane glycoprotein that has been implicated in several processes including angiogenesis and immunity. Recent evidence has also shown that it is implied in the cellular internalization of the severe acute respiratory syndrome coronavirus (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19). We hypothesized that specific microRNAs can target Neuropilin-1. By combining bioinformatic and functional approaches, we identified miR-24 as a regulator of Neuropilin-1 transcription. Since Neuropilin-1 has been shown to play a key role in the endothelium-mediated regulation of the blood-brain barrier, we validated miR-24 as a functional modulator of Neuropilin-1 in human brain microvascular endothelial cells (hBMECs), which are the most suitable cell line for an in vitro blood–brain barrier model.

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miR-24 Targets the Transmembrane Glycoprotein Neuropilin-1 in Human Brain Microvascular Endothelial Cells

Non-Coding RNA ◽

10.3390/ncrna7010009 ◽

2021 ◽

Vol 7 (1) ◽

pp. 9

Author(s):

Pasquale Mone ◽

Jessica Gambardella ◽

Xujun Wang ◽

Stanislovas S. Jankauskas ◽

Alessandro Matarese ◽

...

Keyword(s):

Endothelial Cells ◽

Human Brain ◽

Blood Brain Barrier ◽

Brain Barrier ◽

Microvascular Endothelial Cells ◽

Brain Microvascular Endothelial Cells ◽

Transmembrane Glycoprotein ◽

Blood Brain ◽

Neuropilin 1 ◽

Microvascular Endothelial

Neuropilin-1 is a transmembrane glycoprotein that has been implicated in several processes including angiogenesis and immunity. Recent evidence has also shown that it is implied in the cellular internalization of the severe acute respiratory syndrome coronavirus (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19). We hypothesized that specific microRNAs can target Neuropilin-1. By combining bioinformatic and functional approaches, we identified miR-24 as a regulator of Neuropilin-1 transcription. Since Neuropilin-1 has been shown to play a key role in the endothelium-mediated regulation of the blood-brain barrier, we validated miR-24 as a functional modulator of Neuropilin-1 in human brain microvascular endothelial cells (hBMECs), which are the most suitable cell line for an in vitro blood–brain barrier model.

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Anthropogenic Iron Oxide Nanoparticles Induce Damage to Brain Microvascular Endothelial Cells Forming the Blood-Brain Barrier

Advances in Alzheimer’s Disease - Alzheimer’s Disease and Air Pollution ◽

10.3233/aiad210010 ◽

2021 ◽

Author(s):

Lorena Gárate-Vélez ◽

Claudia Escudero-Lourdes ◽

Daniela Salado-Leza ◽

Armando González-Sánchez ◽

Ildemar Alvarado-Morales ◽

...

Keyword(s):

Endothelial Cells ◽

Blood Brain Barrier ◽

Brain Barrier ◽

Microvascular Endothelial Cells ◽

Brain Microvascular Endothelial Cells ◽

Blood Brain ◽

Fe3o4 Nps ◽

Microvascular Endothelial ◽

The Brain

Background: Iron nanoparticles, mainly in magnetite phase (Fe3O4 NPs), are released to the environment in areas with high traffic density and braking frequency. Fe3O4 NPs were found in postmortem human brains and are assumed to get directly into the brain through the olfactory nerve. However, these pollution-derived NPs may also translocate from the lungs to the bloodstream and then, through the blood-brain barrier (BBB), into the brain inducing oxidative and inflammatory responses that contribute to neurodegeneration. Objective: To describe the interaction and toxicity of pollution-derived Fe3O4 NPs on primary rat brain microvascular endothelial cells (rBMECs), main constituents of in vitro BBB models. Methods: Synthetic bare Fe3O4 NPs that mimic the environmental ones (miFe3O4) were synthesized by co-precipitation and characterized using complementary techniques. The rBMECs were cultured in Transwell® plates. The NPs-cell interaction was evaluated through transmission electron microscopy and standard colorimetric in vitro assays. Results: The miFe3O4 NPs, with a mean diameter of 8.45 ± 0.14 nm, presented both magnetite and maghemite phases, and showed super-paramagnetic properties. Results suggest that miFe3O4 NPs are internalized by rBMECs through endocytosis and that they are able to cross the cells monolayer. The lowest miFe3O4 NPs concentration tested induced mid cytotoxicity in terms of 1) membrane integrity (LDH release) and 2) metabolic activity (MTS transformation). Conclusion: Pollution-derived Fe3O4 NPs may interact and cross the microvascular endothelial cells forming the BBB and cause biological damage.

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