miR199a3p suppresses cervical epithelial cell inflammation by inhibiting the HMGB1/TLR4/NFκB pathway in preterm birth.
Mol Med Rep
; 22(2): 926-938, 2020 08.
Article
em En
| MEDLINE
| ID: mdl-32468045
ABSTRACT
Preterm birth (PTB) is the primary cause of neonatal mortality worldwide. Infection and inflammation are considered to be the primary causes of PTB. Cervical remodeling is an important step in the process of preterm delivery, and the destruction of the cervical epithelial barrier and inflammation are important triggers of cervical remodeling. The aim of the present study was to determine the effect and underlying mechanism of microRNA (miR)199a3p/highmobility group box 1 protein (HMGB1) signaling in cervical epithelial inflammation in PTB. The results of this study revealed that miR199a3p was significantly decreased in cervical epithelial tissue samples from patients in both the preterm labor and preterm premature rupture of membrane groups. This decrease was also observed in tissue samples from a lipopolysaccharide (LPS)induced PTB mouse model and in LPSinduced ectocervical and endocervical cells. Whereas, the expression of HMGB1 and tolllike receptor 4 (TLR4) was significantly increased, which was associated with the upregulation of interleukin (IL)1ß and tumor necrosis factor (TNF)α expression. Furthermore, overexpression of miR199a3p significantly suppressed the expression and activation of HMGB1 and TLR4/NFκB signaling, and decreased the levels of IL1ß and TNFα in vitro and in vivo. Additionally, overexpression of HMGB1 and/or TLR4 reversed the antiinflammatory effects of miR199a3p mimics in vitro and in vivo. These results indicate that miR199a3p acts as a negative inflammatory regulator in PTB by targeting HMGB1 to regulate the TLR4/NFκB pathway.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Colo do Útero
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MicroRNAs
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Nascimento Prematuro
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
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Pregnancy
Idioma:
En
Revista:
Mol Med Rep
Ano de publicação:
2020
Tipo de documento:
Article