Zhao Chun, Zhang Ting, Shi Zhonghua, Ding Hongjuan, Ling Xiufeng
State Key Laboratory of Reproductive Medicine, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210004, P.R. China.
Wuxi Maternity and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214002, P.R. China.
Mol Med Rep. 2014 Jun;9(6):2085-90. doi: 10.3892/mmr.2014.2058. Epub 2014 Mar 17.
The placenta is thought to have a critical role in the pathogenesis of gestational diabetes mellitus (GDM), as GDM‑associated complications resolve following delivery. Placenta-specific microRNAs (miRNAs) may contribute to the pathology of the development of GDM. The aim of the present study was to evaluate whether the placenta-specific miR-518d contributes to the development of GDM. It was revealed that miR-518d expression was higher in placentas taken from patients with GDM compared with control placentas, whereas the protein levels of the predicted miR-518d target gene, peroxisome proliferator-activated receptor-α (PPARα), were lower in placentas from patients with GDM compared with those from control subjects. It was also demonstrated that PPARα was a direct target of miR-518d with a specific binding site at the seed sequence, which determines target specificity. In the placentas of females with GDM increased levels of miR-518d were negatively correlated with the levels of PPARα protein. As PPARα dysregulation may be related to the development of GDM, it is suggested that upregulation of miR-518d may be associated with the pathogenesis of GDM via an effect on the regulation of PPARα expression.
胎盘被认为在妊娠期糖尿病(GDM)的发病机制中起关键作用,因为与GDM相关的并发症在分娩后会消退。胎盘特异性微小RNA(miRNA)可能有助于GDM发生发展的病理过程。本研究的目的是评估胎盘特异性miR-518d是否有助于GDM的发生发展。结果显示,与对照胎盘相比,取自GDM患者的胎盘组织中miR-518d表达更高,而预测的miR-518d靶基因过氧化物酶体增殖物激活受体-α(PPARα)的蛋白水平在GDM患者的胎盘中低于对照受试者。研究还表明,PPARα是miR-518d的直接靶标,在决定靶标特异性的种子序列处具有特异性结合位点。在患有GDM的女性胎盘中,miR-518d水平升高与PPARα蛋白水平呈负相关。由于PPARα失调可能与GDM的发生发展有关,因此提示miR-518d的上调可能通过影响PPARα表达的调控而与GDM的发病机制相关。