Agricultural Ministry Key Laboratory of Swine Breeding and Genetics & Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, China.
Int J Mol Sci. 2022 Feb 7;23(3):1864. doi: 10.3390/ijms23031864.
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 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 -dependent p38 and JNK signaling pathways to cause preterm birth.
分娩是一个涉及胎儿和母体两部分的炎症和激素变化过程。miR-132-3p（miR-132-3p）已被报道参与炎症相关疾病的发展。然而，其在分娩开始中的潜在作用知之甚少。本研究旨在探讨 miR-132-3p 在胎膜分娩中的作用机制。在小鼠胎膜膜中，发现 miR-132-3p 的表达在妊娠晚期逐渐增加。在人羊膜上皮细胞系（WISH）中，上调 miR-132-3p 增加促炎细胞因子和环氧化酶 2（COX2）以及前列腺素 E2（PGE2），而 miR-132-3p 抑制剂则抑制其表达。双特异性磷酸酶 9（DUSP9）被鉴定为 miR-132-3p 的新靶基因，可被 miR-132-3p 负调控。DUSP9 存在于小鼠胎膜上皮细胞中，在妊娠 18.5 天（dpc）时相对妊娠 15.5 天（dpc）时其丰度降低。沉默促进了 WISH 细胞中促炎细胞因子和 COX2 以及 PGE2 分泌，p38 抑制剂 SB203580 或 JNK 抑制剂 SP600125 可减弱其作用。此外，向妊娠小鼠腹腔内注射 miR-132-3p 激动剂不仅导致早产，还促进了 COX2 以及磷酸化 JNK 和 p38 水平的增加，以及小鼠胎膜中 DUSP9 水平的降低。综上所述，miR-132-3p 可能通过靶向依赖 p38 和 JNK 信号通路参与炎症和 PGE2 释放，导致早产。
