MiR-132-3p Modulates DUSP9-Dependent p38/JNK Signaling Pathways to Enhance Inflammation in the Amnion Leading to Labor.

Zhuxia Zhong,Zezhang Liu,Rong Zheng,Siwen Jiang,Jin Chai

doi:10.3390/ijms23031864

Zhuxia Zhong, Zezhang Liu + Show 3 more

Open Access

https://doi.org/10.3390/ijms23031864

Copy DOI

Abstract

Labor is a process of inflammation and hormonal changes involving both fetal and maternal compartments. MicroRNA-132-3p (miR-132-3p) has been reported to be involved in the development of inflammation-related diseases. However, little is known about its potential role in labor onset. This study aimed to explore the mechanism of miR-132-3p in amnion for labor initiation. In the mouse amnion membranes, the expression of miR-132-3p was found to increase gradually during late gestation. In human amniotic epithelial cell line (WISH), upregulation of miR-132-3p was found to increase proinflammatory cytokines and cyclooxygenase 2 (COX2) as well as prostaglandin E2 (PGE2), which was suppressed by miR-132-3p inhibitor. Dual-specificity phosphatase 9 (DUSP9) was identified as a novel target gene of miR-132-3p, which could be negatively regulated by miR-132-3p. DUSP9 was present in the mouse amnion epithelial cells, with a decrease in its abundance at 18.5 days post coitum (dpc) relative to 15.5 dpc. Silencing DUSP9 was found to facilitate the expression of proinflammatory cytokines and COX2 as well as PGE2 secretion in WISH cells, which could be attenuated by p38 inhibitor SB203580 or JNK inhibitor SP600125. Additionally, intraperitoneal injection of pregnant mice with miR-132-3p agomir not only caused preterm birth, but also promoted the abundance of COX2 as well as phosphorylated JNK and p38 levels, and decreased DUSP9 level in mouse amnion membranes. Collectively, miR-132-3p might participate in inflammation and PGE2 release via targeting DUSP9-dependent p38 and JNK signaling pathways to cause preterm birth.

Highlights

Labor or parturition, an event indicating the end of pregnancy, is a complex physiological process involving interactions between the myometrium and signals derived from fetus, fetal membranes, and placenta [1]
By predicting miR-132-3p binds to Dual-specificity phosphatase 9 (DUSP9), we aimed to investigate how miR-132-3p and its target DUSP9 participate in the regulation of inflammation and prostaglandins for parturition initiation by analyzing their interactions using human amnion epithelial cells and a mouse model
Labor is a process of inflammation [29], and inflammation, which is recognized as the infiltration of immune cells and the production of proinflammatory cytokines, occurs in the cervix, myometrium, and fetal membranes, facilitating cervical remodeling, uterine contractility, and membrane rupture in both term and preterm labor [30,31]

Summary

Introduction

An event indicating the end of pregnancy, is a complex physiological process involving interactions between the myometrium and signals derived from fetus, fetal membranes, and placenta [1]. There is substantial evidence that indicates that fetal membrane-derived signals, including prostaglandins (PGs) and inflammation, are involved in the initiation and progression of parturition [4,5,6,7]. Prostaglandins and inflammation were reported to induce changes in cervical structure, contraction of the uterus, and weakening of fetal membranes at the onset of labor [8]. Understanding the molecular mechanism of prostaglandins and inflammation in fetal membranes during labor may facilitate the prediction or prevention of preterm birth Excessive or premature activation of these signals might cause preterm labor, resulting in maternal and neonatal pathological damages and diseases [9].

Objectives

Methods

Findings

Conclusion