Association of placental PPAR alpha/gamma and miR-27b expression with macrosomia in healthy pregnancy

PEDIATRIC RESEARCH(2023)

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摘要
Background 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. Methods 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. Results The PPAR alpha/gamma 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 PPAR beta, miR-17, and miR-34a. After adjusting for confounding factors, low miR-27b and high PPAR alpha/gamma mRNA expression still increased the risk of macrosomia. The PPAR alpha/gamma protein levels presented a corresponding decrease or increase when cells were transfected with miR-27b mimic or inhibitor. Conclusions Placental PPAR alpha/gamma and miR-27b expression were associated with non-GDM macrosomia and miR-27b probably promotes the occurrence of non-GDM macrosomia by regulating PPAR alpha/gamma protein. Impact Low miR-27b and high 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 PPAR alpha and PPAR gamma protein. MiR-27b was probably involved in non-GDM macrosomia through negative regulation of PPAR alpha/gamma protein.
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