Phosphorylation of Yes-associated protein impairs trophoblast invasion and migration: implications for the pathogenesis of fetal growth restriction†.
Fetal growth restriction (FGR) is a condition in which a newborn fails to achieve his or her prospective hereditary growth potential. This condition is associated with high newborn mortality, second only to that associated with premature birth. FGR is associated with maternal, fetal, and placental abnormalities. Although the placenta is considered to be an important organ for supplying nutrition for fetal growth, research on FGR is limited, and treatment through the placenta remains challenging, as neither proper uterine intervention nor its pathogenesis have been fully elucidated. Yes-associated protein (YAP), as the effector of the Hippo pathway, is widely known to regulate organ growth and cancer development. Therefore, the correlation of the placenta and YAP was investigated to elucidate the pathogenic mechanism of FGR. Placental samples from humans and mice were collected for histological and biomechanical analysis. After investigating the location and role of YAP in the placenta by immunohistochemistry, we observed that YAP and cytokeratin 7 have corresponding locations in human and mouse placentas. Moreover, phosphorylated YAP (p-YAP) was upregulated in FGR and gradually increased as gestational age increased during pregnancy. Cell function experiments and mRNA-Seq demonstrated impaired YAP activity mediated by extracellular signal-regulated kinase inhibition. Established FGR-like mice also recapitulated a number of the features of human FGR. The results of this study may help to elucidate the association of FGR development with YAP and provide an intrauterine target that may be helpful in alleviating placental dysfunction.
['Wang|Hao|H|', 'Xu|Ping|P|', 'Luo|Xiaofang|X|', 'Hu|Mingyu|M|', 'Liu|Yamin|Y|', 'Yang|Yike|Y|', 'Peng|Wei|W|', 'Bai|Yuxiang|Y|', 'Chen|Xuehai|X|', 'Tan|Bin|B|', 'Wu|Yue|Y|', 'Wen|Li|L|', 'Gao|Rufei|R|', 'Tong|Chao|C|', 'Qi|Hongbo|H|', 'Kilby|Mark D|MD|', 'Saffery|Richard|R|', 'Baker|Philip N|PN|']
D048868:Adaptor Proteins, Signal Transducing D000818:Animals D002460:Cell Line D002465:Cell Movement D004622:Embryo, Mammalian D048049:Extracellular Signal-Regulated MAP Kinases D005260:Female D005786:Gene Expression Regulation D006801:Humans D007191:Indazoles D051379:Mice D008810:Mice, Inbred C57BL D010766:Phosphorylation D010879:Piperazines D010920:Placenta D011247:Pregnancy D014157:Transcription Factors D014327:Trophoblasts D015854:Up-Regulation D000091102:YAP-Signaling Proteins
Yes-associated protein trophoblast invasion migration fetal growth restriction placenta