Department of Nutritional Medicine, Interactive Research School for Health Affairs, Bharati Vidyapeeth Deemed University, Pune, Maharashtra, India.
Department of Obstetrics and Gynecology, Bharati Hospital and Research Center, Pune, Maharashtra, India.
IUBMB Life. 2017 Dec;69(12):985-993. doi: 10.1002/iub.1687. Epub 2017 Nov 11.
Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) are crucial to the processes of normal labor and parturition. We have previously reported aberrant protein levels of MMPs in placenta of women delivering preterm as compared to term. In this study, we examine the mRNA levels of MMPs (MMP-1, MMP-2, and MMP-9) and TIMPs (TIMP-1, TIMP-2) in the placenta from women delivering preterm as compared with term and further study the promoter DNA methylation of the MMP-9 gene in a sub-sample of term and preterm placentae. A total of 110 women were included in the study; 56 delivered term and 54 delivered preterm. MMP and TIMP mRNA levels were determined by Taqman-based qPCR. Promoter CpG methylation of MMP-9 gene was studied on a subset of 10 term and 8 preterm placenta using Epitect Methyl-II PCR assay kit. The mRNA levels of MMP-1,-2 were higher and those of TIMP-1,-2 were lower in the placentae of women delivering preterm. MMP-9 levels were comparable between the two groups. Among women undergoing spontaneous vaginal deliveries, higher mRNA levels of MMP-1, -2 and -9 were seen in the placentae of those delivering preterm as compared to term. Similar results were seen in women undergoing preterm labor as compared to term. MMP-9 gene promoter was hypomethylated in preterm placenta as compared to term placenta, while the mRNA levels were comparable between the two groups. The observed imbalance between MMP and TIMP expression may have prematurely triggered the signaling cascade leading to preterm birth. © 2017 IUBMB Life, 69(12):985-993, 2017.
基质金属蛋白酶（MMPs）和基质金属蛋白酶组织抑制剂（TIMPs）对于正常分娩过程至关重要。我们之前曾报道过早产妇女胎盘内 MMPs 蛋白水平异常，与足月产相比。在这项研究中，我们研究了早产妇女胎盘内 MMPs（MMP-1、MMP-2 和 MMP-9）和 TIMPs（TIMP-1、TIMP-2）的 mRNA 水平，并进一步研究了 MMP-9 基因启动子 DNA 甲基化在足月和早产胎盘的亚样本中的情况。共有 110 名妇女参与了这项研究；56 名妇女足月分娩，54 名妇女早产。通过 Taqman 基 qPCR 测定 MMP 和 TIMP mRNA 水平。使用 Epitect Methyl-II PCR 试剂盒研究 MMP-9 基因启动子的 CpG 甲基化，在 10 个足月和 8 个早产胎盘的亚样本中进行。早产妇女胎盘中 MMP-1、-2 的 mRNA 水平较高，而 TIMP-1、-2 的 mRNA 水平较低。两组间 MMP-9 水平无差异。在自发性阴道分娩的妇女中，与足月产相比，早产妇女胎盘中 MMP-1、-2 和 -9 的 mRNA 水平较高。在早产妇女中也观察到与足月产相比类似的结果。与足月胎盘相比，早产胎盘中 MMP-9 基因启动子呈低甲基化状态，而两组间的 mRNA 水平无差异。MMP 和 TIMP 表达的不平衡可能过早地触发了导致早产的信号级联反应。©2017 IUBMB Life，69（12）：985-993，2017。
