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

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.

Identification of Key Candidate Genes and Pathways in Preterm Birth by Integrated Bioinformatical Analysis

“…During labor, the IL1β level is increased due to the influx of leukocytes into intrauterine tissues, which can enhance the contractile potential of myometrial smooth muscle [24 ,25].In addition, it has been demonstrated that IL-1βcan increase prostaglandin production and MMP9 expression via NF-kappa B signaling pathway [26 ,27], which are known to induce cervical ripening and myometrial contractions[ 28 29]. There is higher expression of the subunit of NF-κB in membranes, cervix and myometrium [30,31]. NF-κB can be activated by pro-inflammatory cytokines such as TNF and IL1β, and microbial or viral components that activate toll-like receptors (TLRs) [32].…”

Serum apolipoprotein A-II and alpha-2-antiplasmin levels in midtrimester can be used as predictors of preterm delivery

“… 10 Most spontaneous preterm birth is caused by dominant or subclinical infection of the upper genital tract that results in a host anti-inflammatory response. 11 The destruction of the cervical epithelial barrier and an inflammatory response are important trigger factors for cervical remodelling, which is an important step in preterm delivery. 11 At present, transvaginal cervical tube length measurement is the best method to screen for the risk of premature delivery in pregnancy, but its application is limited, so it is necessary to find better screening indicators.…”

“…11 The destruction of the cervical epithelial barrier and an inflammatory response are important trigger factors for cervical remodelling, which is an important step in preterm delivery. 11 At present, transvaginal cervical tube length measurement is the best method to screen for the risk of premature delivery in pregnancy, but its application is limited, so it is necessary to find better screening indicators. 12 The differentially expressed proteins identified in this present study were mainly from the complement and coagulation cascade pathways.…”

Aconitine Induces TRPV2-Mediated Ca2+ Influx through the p38 MAPK Signal and Promotes Cardiomyocyte Apoptosis

“…The performance of the qRT-PCR assay followed the methods of Peng et al with some modification [ 25 ]. Total RNA was extracted from H9c2 cells using TRIzol reagent (Invitrogen, USA) and then reverse transcribed using a PrimeScript RT reagent kit (Takara Biotechnology Co., Ltd.), following the manufacturer's instructions (with the temperature protocol of 37°C for 15 min and 85°C for 5 sec).…”

“…Western blotting was used to examine the expression levels of proteins in this study; the method followed the methods of Peng et al with some modifications [ 25 ]. Each group of H9c2 cells was harvested and lysed in RIPA buffer with protease inhibitors (Invitrogen, USA), and the protein concentrations were determined by the Pierce BCA assay (Invitrogen, USA), according to the manufacturer's protocols.…”