Inhibition of miR-139-5p by topical JTXK gel promotes healing of Staphylococcus aureus-infected skin wounds.
Cells Dev
; 166: 203658, 2021 06.
Article
em En
| MEDLINE
| ID: mdl-33994349
ABSTRACT
BACKGROUND:
The inflammatory skin wound response is regulated by argonaute 2-bound microRNAs (Ago2-miRNAs) such as miR-139-5p, which inhibit transcription of their target mRNAs. Jiang Tang Xiao Ke (JTXK) is a traditional Chinese medicine that reduces miR-139-5p expression, suggesting that topical application of JTXK may have effects on wound healing.METHODS:
miR-139-/- mice and wild-type (WT) mice were employed to characterize the in vivo effects of miR-139-5p on sterile wound healing. Neutrophil migration and activation into the wound site were examined by live imaging analysis in lys-EGFP mice and myeloperoxidase/aminophenyl fluorescein assays, respectively. In silico and in vitro studies in differentiated HL60 cells were performed to identify miR-139-5p's downstream mediator(s). miR-139-/- neutrophil transplantation (with or without Eif4g2-knockdown rescue) or a topical JTXK gel preparation (with or without miR-139-5p mimic rescue) were employed to characterize the in vivo effects of miR-139-5p and JTXK, respectively, on Staphylococcus aureus (S. aureus)-infected wound healing.RESULTS:
miR-139-/- mice display impaired sterile wound healing but improved S. aureus-infected wound healing. Eif4g2, a protein that supports neutrophil proliferation and differentiation, was identified as a key downstream mediator of miR-139-5p. miR-139-/- mice show elevated neutrophilic activation and Eif4g2 upregulation. miR-139-/- neutrophils enhanced S. aureus-infected wound healing in an Eif4g2-dependent manner. Moreover, topical JTXK gel therapy also enhanced S. aureus-infected wound healing in a miR-139-5p-dependent manner.CONCLUSIONS:
miR-139-5p negatively regulates the neutrophilic response during S. aureus-infected wound healing, suggesting that JTXK or other miR-139-5p suppressants may be effective for treating infected skin wounds.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pele
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Infecções Estafilocócicas
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Staphylococcus aureus
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Cicatrização
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Infecção dos Ferimentos
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Medicamentos de Ervas Chinesas
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MicroRNAs
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Géis
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article