TY - JOUR T1 - Maternal RND3/RhoE deficiency impairs placental mitochondrial function in preeclampsia by modulating PPARγ-UCP2 cascade JF - bioRxiv DO - 10.1101/2020.06.22.164921 SP - 2020.06.22.164921 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 - Xiaojing Yue Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/11/12/2020.06.22.164921.abstract N2 - Preeclampsia (PE) is a life-threatening disease of the pregnant women, and has a profound influence on fetal development. Mitochondrial-mediated placental oxidative stress plays key role in the etiology of PE. However, the underlying mechanism remains to be revealed. Here, we identify Rnd3, a small Rho GTPase, participating in the regulation of placental mitochondrial reactive oxygen species (ROS). We showed that Rnd3 is down-regulated in primary trophoblasts isolated from PE patients. Loss of Rnd3 in trophoblasts resulted in excessive ROS generation, cell apoptosis, mitochondrial injury and proton leakage from respiratory chain. Moreover, Rnd3 overexpression partially rescues the mitochondrial defects and oxidative stress in human PE primary trophoblasts. Mechanistically, Rnd3 physically interacts with the peroxisome proliferators-activated receptor γ (PPARγ) and promotes PPARγ-mitochondrial uncoupling protein 2 (UCP2) cascade. Forced expression of PPARγ rescues deficiency of Rnd3-mediated mitochondrial dysfunction. We conclude that Rnd3 acts as a novel protective factor in placental mitochondria through PPARγ-UCP2 signaling and highlight that downregulation of Rnd3 is a potential factor involved in the pathogenesis of PE.Competing Interest StatementThe authors have declared no competing interest. ER -