Targeting miR-497-5p rescues human keratinocyte dysfunction upon skin exposure to sulfur mustard.
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
10 Aug 2024
10 Aug 2024
Historique:
received:
04
01
2024
accepted:
05
08
2024
revised:
30
07
2024
medline:
11
8
2024
pubmed:
11
8
2024
entrez:
10
8
2024
Statut:
epublish
Résumé
Sulfur mustard (SM) is a highly toxic chemical warfare agent. Exposure to SM results in various pathologies including skin lesions with subsequent impaired wound healing. To date, there are no effective treatments available. Here we discover a SM-triggered pathomechanism involving miR-497-5p and its target survivin which contributes to keratinocyte dysfunction. Transcriptome analysis using RNA-seq in normal human epidermal keratinocytes (NHEK) revealed that SM evoked differential expression of 1896 mRNAs and 25 miRNAs with many of these RNAs known to be involved in keratinocyte function and wound healing. We demonstrated that keratinocyte differentiation and proliferation were efficiently regulated by miRNAs induced in skin cells after exposure to SM. The inhibition of miR-497-5p counteracted SM-induced premature differentiation and stimulated proliferation of NHEK. In addition, we showed that microneedle-mediated transdermal application of lipid-nanoparticles containing miR-497-5p inhibitor restored survivin biosynthesis and cellular functionality upon exposure to SM using human skin biopsies. Our findings expand the current understanding of SM-associated molecular toxicology in keratinocytes and highlight miR-497-5p as feasible clinical target for specific skin therapy in SM-exposed patients and beyond.
Identifiants
pubmed: 39127703
doi: 10.1038/s41419-024-06974-2
pii: 10.1038/s41419-024-06974-2
doi:
Substances chimiques
MicroRNAs
0
Mustard Gas
T8KEC9FH9P
MIRN497 microRNA, human
0
Survivin
0
Chemical Warfare Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
585Subventions
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : RI 808/6-1
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : BA 4925/2-1
Informations de copyright
© 2024. The Author(s).
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