Cell-Crossing Functional Network Driven by microRNA-125a Regulates Endothelial Permeability and Monocyte Trafficking in Acute Inflammation.
endothelial cells
immune cell trafficking
inflammation
microRNA network
monocytes
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2022
2022
Historique:
received:
30
11
2021
accepted:
24
02
2022
entrez:
11
4
2022
pubmed:
12
4
2022
medline:
13
4
2022
Statut:
epublish
Résumé
Opening of the endothelial barrier and targeted infiltration of leukocytes into the affected tissue are hallmarks of the inflammatory response. The molecular mechanisms regulating these processes are still widely elusive. In this study, we elucidate a novel regulatory network, in which miR-125a acts as a central hub that regulates and synchronizes both endothelial barrier permeability and monocyte migration. We found that inflammatory stimulation of endothelial cells induces miR-125a expression, which consecutively inhibits a regulatory network consisting of the two adhesion molecules VE-Cadherin (CDH5) and Claudin-5 (CLDN5), two regulatory tyrosine phosphatases (PTPN1, PPP1CA) and the transcription factor ETS1 eventually leading to the opening of the endothelial barrier. Moreover, under the influence of miR-125a, endothelial expression of the chemokine CCL2, the most predominant ligand for the monocytic chemokine receptor CCR2, was strongly enhanced. In monocytes, on the other hand, we detected markedly repressed expression levels of miR-125a upon inflammatory stimulation. This induced a forced expression of its direct target gene CCR2, entailing a strongly enhanced monocyte chemotaxis. Collectively, cell-type-specific differential expression of miR-125a forms a synergistic functional network controlling monocyte trafficking across the endothelial barrier towards the site of inflammation. In addition to the known mechanism of miRNAs being shuttled between cells
Identifiants
pubmed: 35401562
doi: 10.3389/fimmu.2022.826047
pmc: PMC8986987
doi:
Substances chimiques
MIRN125 microRNA, human
0
MicroRNAs
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
826047Informations de copyright
Copyright © 2022 Müller, Hübner, Li, Tomasi, Ließke, Effinger, Hirschberger, Pogoda, Sperandio and Kreth.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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