PT  - JOURNAL ARTICLE
AU  - Xiaojing Yue
AU  - Liping Huang
AU  - Yanlin Ma
AU  - Lu Chen
AU  - Jiang Chang
AU  - Mei Zhong
AU  - Zhijian Wang
AU  - Ying Sun
AU  - Xia Chen
AU  - Fei Sun
AU  - Lu Xiao
AU  - Jianing Chen
AU  - Yinjun Lai
AU  - Chuming Yan
AU  - Yanhong Yu
TI  - RND3/RhoE deficiency in preeclamptic women impairs placental mitochondrial function via regulation of the PPARgamma-UCP2 pathway
AID  - 10.1101/2020.06.22.164921
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.06.22.164921
4099  - http://biorxiv.org/content/early/2020/06/22/2020.06.22.164921.short
4100  - http://biorxiv.org/content/early/2020/06/22/2020.06.22.164921.full
AB  - Preeclampsia (PE) is a life-threatening hypertensive disorder in pregnancy. Mitochondrial-mediated oxidative stress has been implicated in the etiology of PE with unknown underlying mechanism. We identified the downregulation of Rnd3 in the placental tissues and the primary trophoblasts from PE patients, associated with increased ROS generation and damaged mitochondrial integrity. Knockdown of Rnd3 in trophoblastic cells resulted in mitochondrial injury with membrane potential depolarization and proton leakage. Mechanistic studies indicated that Rnd3 stimulated the mitochondrial uncoupling protein 2 (UCP2) signaling, via its physical interaction with peroxisome proliferators-activated receptor γ (PPARγ). Rnd3 deficiency-mediated mitochondrial dysfunction was attenuated by overexpression of PPARγ. Finally, Rnd3 overexpression in human PE primary trophoblasts partially rescued the mitochondrial defect and oxidative stress. We conclude that Rnd3 acts as a novel protective factor in placental mitochondria through PPARγ-UCP2 signaling. Downregulation of Rnd3 in PE patients may explain the mitochondrial stress involved in the pathogenesis of PE.Competing Interest StatementThe authors have declared no competing interest.