Ni Li-Fang, Han Ying, Wang Shan-Shan, Lin Xiao-Jun, Wang Yu-Huan, Yan Hong-Tao, Yang Xin-Jun
Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, 325035, Wenzhou, Zhejiang, P. R. China.
Department of Obstetrics, The 2nd Affiliated Hospital of Wenzhou Medical University, 325035, Wenzhou, Zhejiang, P. R. China.
Pediatr Res. 2023 Jan;93(1):267-273. doi: 10.1038/s41390-022-02072-1. Epub 2022 Apr 22.
Peroxisomal proliferator-activated receptors (PPARs) and microRNAs (miRNAs) play important roles in the development of fetuses, whereas expression changes of PPARs and three miRNAs (miR-17, miR-27b and miR-34a) and whether these miRNAs regulate PPARs in non-GDM macrosomia placenta is unclear.
A case-control study was performed to collect information and placental tissues on mothers and newborns of non-GDM macrosomia and normal-birth-weight infants. In vitro HTR8-SVneo cellular model was used to detect the effects of miRNAs on PPARs expression. Quantitative real-time PCR (qRT-PCR) and western blot was applied to examine the expression levels of PPARs, miR-17, miR-27b, and miR-34a in placental tissues and cells.
The PPARα/γ mRNA and protein levels were significantly up-regulated and miR-27b was down-regulated in the placenta of macrosomia group compared with in the control group, while no difference was observed in PPARβ, miR-17, and miR-34a. After adjusting for confounding factors, low miR-27b and high PPARα/γ mRNA expression still increased the risk of macrosomia. The PPARα/γ protein levels presented a corresponding decrease or increase when cells were transfected with miR-27b mimic or inhibitor.
Placental PPARα/γ and miR-27b expression were associated with non-GDM macrosomia and miR-27b probably promotes the occurrence of non-GDM macrosomia by regulating PPARα/γ protein.
Low miR-27b and high PPARα/γ mRNA expression in the placenta were associated with higher risk of macrosomia. In vitro HTR8-SVneo cell experiment supported that miR-27b could negatively regulate the expression of PPARα and PPARγ protein. MiR-27b was probably involved in non-GDM macrosomia through negative regulation of PPARα/γ protein.
过氧化物酶体增殖物激活受体(PPARs)和微小RNA(miRNAs)在胎儿发育中起重要作用,然而,在非妊娠期糖尿病(GDM)巨大儿胎盘组织中,PPARs及三种miRNAs(miR-17、miR-27b和miR-34a)的表达变化以及这些miRNAs是否调控PPARs尚不清楚。
进行一项病例对照研究,收集非GDM巨大儿和正常出生体重儿母亲及新生儿的信息和胎盘组织。采用体外HTR8-SVneo细胞模型检测miRNAs对PPARs表达的影响。运用定量实时聚合酶链反应(qRT-PCR)和蛋白质免疫印迹法检测胎盘组织和细胞中PPARs、miR-17、miR-27b和miR-34a的表达水平。
与对照组相比,巨大儿组胎盘组织中PPARα/γ的mRNA和蛋白水平显著上调,miR-27b表达下调,而PPARβ、miR-17和miR-34a无差异。校正混杂因素后,低水平miR-27b和高水平PPARα/γ mRNA表达仍增加巨大儿发生风险。当用miR-27b模拟物或抑制剂转染细胞时,PPARα/γ蛋白水平相应降低或升高。
胎盘组织中PPARα/γ和miR-27b表达与非GDM巨大儿相关,miR-27b可能通过调控PPARα/γ蛋白促进非GDM巨大儿的发生。
胎盘组织中低水平miR-27b和高水平PPARα/γ mRNA表达与巨大儿发生风险较高相关。体外HTR8-SVneo细胞实验支持miR-27b可负向调控PPARα和PPARγ蛋白表达。miR-27b可能通过对PPARα/γ蛋白的负向调控参与非GDM巨大儿的发生。