RhoB/ROCK mediates oxygen-glucose deprivation-stimulated syncytiotrophoblast microparticle shedding in preeclampsia.
Increased circulating syncytiotrophoblast microparticles (STBMs) are often associated with preeclampsia (PE) but the molecular mechanisms regulating STBM shedding remain elusive. Experimental evidence has shown that actin plays a key role in STBM shedding and that Rho/ROCK is important in regulating actin rearrangement. To investigate the role of RhoB/ROCK-regulated actin arrangement in STBM shedding in PE, chorionic villous explants were prepared from placenta of patients with normotensive or PE pregnancies and BeWo cells were fused to imitate syncytiotrophoblasts. The oxygen-glucose deprivation (OGD) conditions were applied to imitate the pathophysiology of PE in vitro. The results showed that RhoB and ROCK were activated in the preeclamptic placenta, accompanied by increased actin polymerization and decreased outgrowing microvilli. In villous tissue cultures or BeWo cells, OGD activated RhoB, ROCK1 and ROCK2 and promoted STBM shedding and actin stress fibers formation. In BeWo cells, RhoB overexpression activated ROCK1 and ROCK2, leading to F-actin redistribution and STBM shedding and the OGD-induced actin polymerization and STBM shedding could be reversed by RhoB or ROCK knockdown. These results reveal that RhoB and ROCK play a key role in PE by targeting STBM shedding through actin rearrangement and that RhoB/ROCK intervention may be a potential therapeutic strategy for PE.
Department of Obstetrics and Gynecology, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, 10 Changjiangzhilu, Daping, Yuzhong District, Chongqing, 400042, China.
Jian
J
Han
Department of Obstetrics and Gynecology, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, 10 Changjiangzhilu, Daping, Yuzhong District, Chongqing, 400042, China.
Bo-Ping
BP
Yang
Department of Obstetrics and Gynecology, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, 10 Changjiangzhilu, Daping, Yuzhong District, Chongqing, 400042, China.
Yi-Lin
YL
Li
Department of Obstetrics and Gynecology, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, 10 Changjiangzhilu, Daping, Yuzhong District, Chongqing, 400042, China.
Hong-Mei
HM
Li
Department of Obstetrics and Gynecology, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, 10 Changjiangzhilu, Daping, Yuzhong District, Chongqing, 400042, China.
Xiu-Hui
XH
Zheng
Department of Obstetrics and Gynecology, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, 10 Changjiangzhilu, Daping, Yuzhong District, Chongqing, 400042, China.
Li-Li
LL
Yu
Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, The Third Military Medical University, Chongqing, 400038, China.
Qiong
Q
Zhang
Department of Obstetrics and Gynecology, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, 10 Changjiangzhilu, Daping, Yuzhong District, Chongqing, 400042, China.
Ying-Ru
YR
Zheng
Department of Obstetrics and Gynecology, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, 10 Changjiangzhilu, Daping, Yuzhong District, Chongqing, 400042, China.
Ping
P
Yi
Department of Obstetrics and Gynecology, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, 10 Changjiangzhilu, Daping, Yuzhong District, Chongqing, 400042, China. cqlili@tmmu.edu.cn.
Li
L
Li
Department of Obstetrics and Gynecology, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, 10 Changjiangzhilu, Daping, Yuzhong District, Chongqing, 400042, China. gjx_tmmu_obgyn@163.com.
Jian-Xin
JX
Guo
Department of Molecular Biology, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Chongqing, 400042, China.
Yuan-Guo
YG
Zhou
D000199:Actins / Q000378:metabolism; D017209:Apoptosis; D045744:Cell Line, Tumor; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D005947:Glucose / Q000172:deficiency*; D006801:Humans; D008871:Microvilli / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology*; D058105:Polymerization; D011225:Pre-Eclampsia / Q000378:metabolism* / Q000473:pathology*; D011247:Pregnancy; D014327:Trophoblasts / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000378:metabolism*; D020743:rhoB GTP-Binding Protein / Q000378:metabolism*
D000199:Actins; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases; D020743:rhoB GTP-Binding Protein; D005947:Glucose; D010100:Oxygen
Actin; Oxygen-glucose deprivation; Preeclampsia; RhoB; Syncytiotrophoblast microvillous membranes