Maternal RND3/RhoE deficiency impairs placental mitochondrial function in preeclampsia by modulating the PPARγ‐UCP2 cascade
| Autor: | Jiang Chang, Ying Sun, Mei Zhong, Yingjun Lai, Yanlin Ma, Lu Chen, Lu Xiao, Chuming Yan, Liping Huang, Zhijian Wang, Xiaojing Yue, Xia Chen, Fei Sun, Jianing Chen |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
rho GTP-Binding Proteins
0301 basic medicine Placenta Respiratory chain Mitochondrion medicine.disease_cause Biochemistry Pathogenesis 03 medical and health sciences 0302 clinical medicine Pre-Eclampsia Downregulation and upregulation Pregnancy Genetics medicine Humans Uncoupling Protein 2 Molecular Biology chemistry.chemical_classification Reactive oxygen species Rnd3 Mitochondria Trophoblasts Cell biology PPAR gamma Oxidative Stress 030104 developmental biology chemistry Apoptosis Female 030217 neurology & neurosurgery Oxidative stress Biotechnology |
| Zdroj: | The FASEB Journal. 35 |
| ISSN: | 1530-6860 0892-6638 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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