24
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

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

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          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.

          Related collections

          Most cited references44

          • Record: found
          • Abstract: found
          • Article: not found

          Inflammation and pregnancy.

          Inflammation is a process by which tissues respond to various insults. It is characterized by upregulation of chemokines, cytokines, and pattern recognition receptors that sense microbes and tissue breakdown products. During pregnancy, the balance of Th1 (cell-mediated immunity) and Th2 (humoral immunity) cytokines is characterized by an initial prevalence of Th2 cytokines, followed by a progressive shift toward Th1 predominance late in gestation, that when is abnormal, may initiate and intensify the cascade of inflammatory cytokine production involved in adverse pregnancy outcomes. Maternal and placental hormones may affect the inflammatory pathway. Hypoxia and the innate immune response are 2 adaptive mechanisms by which organisms respond to perturbation in organ function, playing a major role in spontaneous abortion, intrauterine growth restriction, preeclampsia, and preterm delivery. The interaction between tissue remodeling factors, like matrix metalloproteinases, and vasoactive/hemostatic factors, like prostaglandin and coagulation factors, mediates this adaptive response.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            HMGB1 release induced by liver ischemia involves Toll-like receptor 4–dependent reactive oxygen species production and calcium-mediated signaling

            Ischemic tissues require mechanisms to alert the immune system of impending cell damage. The nuclear protein high-mobility group box 1 (HMGB1) can activate inflammatory pathways when released from ischemic cells. We elucidate the mechanism by which HMGB1, one of the key alarm molecules released during liver ischemia/reperfusion (I/R), is mobilized in response to hypoxia. HMGB1 release from cultured hepatocytes was found to be an active process regulated by reactive oxygen species (ROS). Optimal production of ROS and subsequent HMGB1 release by hypoxic hepatocytes required intact Toll-like receptor (TLR) 4 signaling. To elucidate the downstream signaling pathways involved in hypoxia-induced HMGB1 release from hepatocytes, we examined the role of calcium signaling in this process. HMGB1 release induced by oxidative stress was markedly reduced by inhibition of calcium/calmodulin-dependent kinases (CaMKs), a family of proteins involved in a wide range of calcium-linked signaling events. In addition, CaMK inhibition substantially decreased liver damage after I/R and resulted in accumulation of HMGB1 in the cytoplasm of hepatocytes. Collectively, these results demonstrate that hypoxia-induced HMGB1 release by hepatocytes is an active, regulated process that occurs through a mechanism promoted by TLR4-dependent ROS production and downstream CaMK-mediated signaling.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Inflammation and preterm birth.

              Preterm birth is the leading cause of neonatal morbidity and mortality. Although the underlying causes of pregnancy-associated complication are numerous, it is well established that infection and inflammation represent a highly significant risk factor in preterm birth. However, despite the clinical and public health significance, infectious agents, molecular trigger(s), and immune pathways underlying the pathogenesis of preterm birth remain underdefined and represent a major gap in knowledge. Here, we provide an overview of recent clinical and animal model data focused on the interplay between infection-driven inflammation and induction of preterm birth. Furthermore, here, we highlight the critical gaps in knowledge that warrant future investigations into the interplay between immune responses and induction of preterm birth.
                Bookmark

                Author and article information

                Journal
                Mol Med Rep
                Mol Med Rep
                Molecular Medicine Reports
                D.A. Spandidos
                1791-2997
                1791-3004
                August 2020
                22 May 2020
                22 May 2020
                : 22
                : 2
                : 926-938
                Affiliations
                [1 ]Department of Obstetrics, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan 650031, P.R. China
                [2 ]Department of Obstetrics, The First Peoples Hospital of Yunnan Province, Kunming, Yunnan 650031, P.R. China
                [3 ]Medicine Faculty of Kunming University of Science and Technology, Kunming, Yunnan 650031, P.R. China
                Author notes
                Correspondence to: Dr Xudong Dong, Department of Obstetrics, The Affiliated Hospital of Kunming University of Science and Technology, The First Peoples Hospital of Yunnan Province, 157 Jinbi Road, Xishan, Kunming, Yunnan 650031, P.R. China, E-mail: dxdkhck@ 123456163.com
                Article
                MMR-22-02-0926
                10.3892/mmr.2020.11184
                7339783
                32468045
                ea678834-1990-4b59-9af3-4096f5f6a8c7
                Copyright: © Peng et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 03 September 2019
                : 09 April 2020
                Categories
                Articles

                microrna-199a-3p,preterm birth,cervical epithelial cells,high-mobility group box 1 protein,inflammation,toll-like receptor 4/nf-κb pathway

                Comments

                Comment on this article

                scite_
                0
                0
                0
                0
                Smart Citations
                0
                0
                0
                0
                Citing PublicationsSupportingMentioningContrasting
                View Citations

                See how this article has been cited at scite.ai

                scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.

                Similar content578

                Cited by8

                Most referenced authors905