Study on the mechanism of PPARγ-Targeted intervention in abnormal lipid Metabolism-Induced dysfunction in placental trophoblast cells in preeclampsia and its clinical relevance
10.3969/j.issn.1006-5725.2025.16.008
- VernacularTitle:基于过氧化物酶体增殖物激活受体γ干预对子痫前期胎盘滋养细胞脂质代谢异常致功能失调机制及临床关联
- Author:
Jingrui LI
1
;
Yaoyu SUO
;
Tian TIAN
;
Ping CAO
;
Zhifeng DONG
;
Nan JIANG
;
Huiping ZHANG
;
Kai WU
;
Qing SHI
;
Guizhong LI
Author Information
1. 宁夏医科大学国家卫生健康委员会代谢性心血管疾病研究重点实验室(宁夏 银川 750004)
- Publication Type:Journal Article
- Keywords:
preeclampsia;
lipid metabolism;
HTR-8/SVneo;
PPAR;
Post-translational phosphorylation
- From:
The Journal of Practical Medicine
2025;41(16):2489-2497
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the causal relationship between abnormal placental lipid metabolism and trophoblast dysfunction in patients with preeclampsia(PE),and to explore the regulatory effects of PPARγ on trophoblast function under hypoxic conditions.Methods Placental tissues were collected from 30 patients with PE and 30 individuals with normal pregnancies at the General Hospital of Ningxia Medical University between October 2020 and November 2021 for the analysis of lipid deposition.A rat model of PE was established,comprising a sham-operated(Sham)group and a reduced uterine perfusion pressure(Rupp)group,with six rats in each group(n=12 total).Human trophoblast cells(HTR-8/SVneo)were cultured in vitro and randomly assigned to four experimental groups:normoxic control,hypoxia,hypoxia+PPARγ agonist(Rosiglitazone),and hypoxia+PPARγ antagonist(T0070907).The expression levels of lipid metabolism-related genes and transcription factors(FASN,FABP4,PPARγ,LXRα)were assessed using RT-qPCR.Western blotting was performed to determine the protein expression levels of PPARγ.Cell migration and invasion capacities were evaluated using scratch wound healing and Transwell assays,respectively.Results Placental lipid deposition in the PE group was significantly higher than that in the control group,particularly in the Rupp model mice(P<0.001).Under hypoxic conditions,the expression levels of FASN and FABP4 were upregulated in trophoblast cells(P<0.001),whereas the expression of PPARγ and LXRα was downregulated(P<0.001).Furthermore,treatment with the PPARγ antagonist T0070907 exacerbated the inhibitory effects of hypoxia on cell function(P<0.001),significantly reducing cell invasion and migration capacity(P<0.001).Additional siRNA-mediated knockdown experiments confirmed that PPARγ deficiency further aggravated hypoxia-induced impairments in cell migration and invasion,and this detrimental effect could not be reversed by Rosiglitazone.Conclusions Abnormal placental lipid metabolism in PE is closely linked to PPARγ-mediated enhancement of lipid synthesis and metabolic dysregulation under hypoxic conditions,which may subsequently impair trophoblast invasion and migration.
