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Published on: June 24, 2020
miR‑199a‑3p suppresses cervical epithelial cell inflammation by inhibiting the HMGB1/TLR4/NF‑κB pathway in preterm
Juan Peng1, Jiang Jiang1, Huizi Wang1
1Department of Obstetrics, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan 650031, P.R. China.
Insights
MicroRNA-199a-3p protects against preterm birth by reducing cervical inflammation. This microRNA targets HMGB1 protein, thereby regulating the TLR4/NF-κB pathway and decreasing inflammatory markers.
Area of Science:
- Reproductive Biology
- Molecular Biology
- Immunology
Background:
- Preterm birth (PTB) is a leading cause of neonatal mortality globally.
- Infection and inflammation are key drivers of PTB, involving cervical remodeling.
- Cervical epithelial barrier disruption and inflammation trigger cervical remodeling.
Purpose of the Study:
- To investigate the role and mechanism of microRNA (miR)-199a-3p/high-mobility group box 1 protein (HMGB1) signaling in cervical epithelial inflammation in PTB.
- To elucidate the regulatory pathway involving miR-199a-3p, HMGB1, and TLR4/NF-κB in the context of PTB.
Main Methods:
- Quantification of miR-199a-3p, HMGB1, TLR4, IL-1β, and TNF-α in human cervical tissues and LPS-induced mouse models.
- In vitro and in vivo experiments involving overexpression of miR-199a-3p, HMGB1, and TLR4.
- Analysis of the TLR4/NF-κB signaling pathway activation.
Main Results:
- miR-199a-3p was significantly decreased in PTB patient tissues and LPS-induced models.
- HMGB1 and TLR4 expression increased, correlating with elevated IL-1β and TNF-α.
- miR-199a-3p overexpression suppressed HMGB1, TLR4/NF-κB signaling, and inflammatory cytokines.
- HMGB1 or TLR4 overexpression counteracted the anti-inflammatory effects of miR-199a-3p.
Conclusions:
- miR-199a-3p functions as a negative regulator of inflammation in PTB.
- It exerts its anti-inflammatory effects by targeting HMGB1 and modulating the TLR4/NF-κB pathway.
- This microRNA represents a potential therapeutic target for managing PTB-associated inflammation.
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)‑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.
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