MicroRNA-125a suppresses intestinal mucosal inflammation through targeting ETS-1 in patients with inflammatory bowel diseases.
J Autoimmun
; 101: 109-120, 2019 07.
Article
em En
| MEDLINE
| ID: mdl-31014918
ABSTRACT
MicroRNA (miR)-125a is highly expressed in T cells and regulates the functions of Treg through the IL-6-STAT3 signaling pathway. However, the role of miR-125a in regulating immune responses in intestinal mucosa of patients with inflammatory bowel diseases (IBD) is still not understood. Here we showed that miR-125a expression was decreased in PBMC and inflamed intestinal mucosa from IBD patients compared with that in healthy controls. Transduction with LV-miR-125a into IBD CD4+ T cells could significantly inhibit proinflammatory cytokine production, including IFN-γ, TNF-α and IL-17A. RNA-seq analysis of miR-125a-/- CD4+ T cells revealed enhanced genes (e.g., Stat1, Stat3, RORγt, Irf4, Klf13) in T cell activation and effector pathways, while ETS-1 as its functional target promoted IBD CD4+ T cell differentiation into Th1 cells. Consistently, miR-125a-/- mice developed more severe colitis induced by TNBS compared with WT mice. Thus, our data suggest that miR-125a protects intestinal mucosa from inflammatory injury and that ETS-1 as its target participates in the pathogenesis of IBD.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doenças Inflamatórias Intestinais
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Regulação Neoplásica da Expressão Gênica
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MicroRNAs
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Interferência de RNA
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Proteína Proto-Oncogênica c-ets-1
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article