miR‑199a‑3p suppresses cervical epithelial cell inflammation by inhibiting the HMGB1/TLR4/NF‑κB pathway in preterm birth

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)‑199a‑3p/high‑mobility group box 1 protein (HMGB1) signaling in cervical epithelial inflammation in PTB. The results of this study revealed that miR‑199a‑3p 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 LPS‑induced ectocervical and endocervical cells. Whereas, the expression of HMGB1 and toll‑like receptor 4 (TLR4) was significantly increased, which was associated with the upregulation of interleukin (IL)‑1β and tumor necrosis factor (TNF)‑α expression. Furthermore, overexpression of miR‑199a‑3p significantly suppressed the expression and activation of HMGB1 and TLR4/NF‑κB signaling, and decreased the levels of IL‑1β and TNF‑α in vitro and in vivo. Additionally, overexpression of HMGB1 and/or TLR4 reversed the anti‑inflammatory effects of miR‑199a‑3p mimics in vitro and in vivo. These results indicate that miR‑199a‑3p acts as a negative inflammatory regulator in PTB by targeting HMGB1 to regulate the TLR4/NF‑κB pathway.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:22

Enthalten in:

Molecular medicine reports - 22(2020), 2 vom: 01. Aug., Seite 926-938

Sprache:

Englisch

Beteiligte Personen:

Peng, Juan [VerfasserIn]
Jiang, Jiang [VerfasserIn]
Wang, Huizi [VerfasserIn]
Feng, Xinzi [VerfasserIn]
Dong, Xudong [VerfasserIn]

Links:

Volltext

Themen:

Cervical epithelial cells
HMGB1 Protein
High-mobility group box 1 protein
Inflammation
Interleukin-1beta
Journal Article
Lipopolysaccharides
MicroRNAs
Microrna-199a-3p
Mirn199 microRNA, human
Mirn199 microRNA, mouse
NF-kappa B
Preterm birth
Toll-Like Receptor 4
Toll-like receptor 4/nF-κB pathway
Tumor Necrosis Factor-alpha

Anmerkungen:

Date Completed 16.03.2021

Date Revised 29.09.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.3892/mmr.2020.11184

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM310485746