iRHOM2 regulates inflammation and endothelial barrier permeability via CX3CL1.
C-X3-C motif chemokine ligand 1
acute lung injury
inactive rhomboid-like protein 2
inflammation
oxidative stress
Journal
Experimental and therapeutic medicine
ISSN: 1792-1015
Titre abrégé: Exp Ther Med
Pays: Greece
ID NLM: 101531947
Informations de publication
Date de publication:
Jul 2023
Jul 2023
Historique:
received:
14
09
2022
accepted:
16
02
2023
medline:
5
6
2023
pubmed:
5
6
2023
entrez:
5
6
2023
Statut:
epublish
Résumé
Acute lung injury (ALI) is associated with increased lung inflammation and lung permeability. The present study aimed to determine the role of inactive rhomboid-like protein 2 (iRHOM2) in ALI in lipopolysaccharide (LPS)-induced pulmonary microvascular endothelial cell model. Human pulmonary microvascular endothelial cells (HPMVECs) were transfected with small interfering RNA targeting iRHOM2 and C-X3-C motif chemokine ligand 1 (CX3CL1) overexpression plasmids and treated with LPS. Cell viability was detected using a Cell Counting Kit-8 assay, while levels of TNFα, IL-1β, IL-6 and p65 were measured by reverse transcription-quantitative PCR and western blotting. Apoptosis levels were measured using a TUNEL assay. Endothelial barrier permeability was detected, followed by analysis of zonula occludens-1, vascular endothelial-cadherin and occludin by immunofluorescence staining or western blotting. The interaction of iRHOM2 and CX3CL1 was analyzed using an immune-coprecipitation assay. Through bioinformatics analysis, it was found that CX3CL1 was upregulated in the LPS group compared with the control. Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that the TNF signaling pathway affected by iRHOM2 and cytokine-cytokine receptor interaction, including CX3CL1, served a key role in ALI. HPMVECs treated with LPS exhibited a decrease in cell viability and an increase in inflammation, apoptosis and endothelial barrier permeability, while these effects were reversed by iRHOM2 silencing. However, CX3CL1 overexpression inhibited the effects of iRHOM2 silencing on LPS-treated HPMVECs. The present study demonstrated a novel role of iRHOM2 as a regulator that affects inflammation, apoptosis and endothelial barrier permeability; this was associated with CX3CL1.
Identifiants
pubmed: 37273752
doi: 10.3892/etm.2023.12018
pii: ETM-26-1-12018
pmc: PMC10236134
doi:
Types de publication
Journal Article
Langues
eng
Pagination
319Informations de copyright
Copyright: © Yan et al.
Déclaration de conflit d'intérêts
The authors declare that they have no competing interests.
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