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Maternal RND3/RhoE deficiency impairs placental mitochondrial function in preeclampsia by modulating the PPARγ‐UCP2 cascade
Author(s) -
Huang Liping,
Ma Yanlin,
Chen Lu,
Chang Jiang,
Zhong Mei,
Wang Zhijian,
Sun Ying,
Chen Xia,
Sun Fei,
Xiao Lu,
Chen Jianing,
Lai Yingjun,
Yan Chuming,
Yue Xiaojing
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202002639rrr
Subject(s) - oxidative stress , mitochondrion , downregulation and upregulation , microbiology and biotechnology , pathogenesis , reactive oxygen species , preeclampsia , mitochondrial respiratory chain , biology , chemistry , immunology , endocrinology , biochemistry , genetics , pregnancy , gene
Preeclampsia (PE) is a life‐threatening disease of pregnant women associated with severe hypertension, proteinuria, or multi‐organ injuries. Mitochondrial‐mediated placental oxidative stress plays a key role in the pathogenesis of PE. However, the underlying mechanism remains to be revealed. Here, we identify Rnd3, a small Rho GTPase, regulating 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 the respiratory chain. Moreover, Rnd3 overexpression partially rescues the mitochondrial defects and oxidative stress in human PE primary trophoblasts. Rnd3 physically interacts with the peroxisome proliferators‐activated receptor γ (PPARγ) and promotes the 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 PE pathogenesis.