miR-16 inhibits the proliferation and angiogenesis-regulating potential of mesenchymal stem cells in severe pre-eclampsia.
Pre-eclampsia is thought to be a systemic disease of maternal endothelial cell dysfunctions. miRNAs regulate various basic biological functions in cells, including stem cells. Mesenchymal stem cells exist in almost all tissues and are the key cellular source for tissue repair and regeneration. Our aims are to investigate whether miRNAs regulate MSCs in fetal-maternal interfaces to influence the pathogenesis of pre-eclampsia. The differential expression of miRNAs in decidua-derived mesenchymal stem cells of all patients with severe pre-eclampsia (n = 20) and normal groups (n = 20) was first screened by microarray analysis and validated by quantitative real-time PCR analysis. The integrated bioinformatics analysis showed that miR-16 showed the highest number of connections in the miRNA GO network and the miRNA gene network. Moreover, over-expressed miR-16 inhibited the proliferation and migration of decidua-derived mesenchymal stem cells and induced cell-cycle arrest by targeting cyclin E1. Interestingly, over-expression of miR-16 by decidua-derived mesenchymal stem cells reduced the ability of human umbilical vein endothelial cells to form blood vessels and reduced the migration of trophoblast cells. Furthermore, decidua-derived mesenchymal stem cell-expressed endothelial growth factor VEGF-A was involved in migration of trophoblast cells and human umbilical vein endothelial cells as well as tube and network formation. Importantly, the levels of cyclin E1 and VEGF-A were negatively correlated with the level of miR-16 expression in decidua-derived mesenchymal stem cells from the patients with severe pre-eclampsia. Together, these data suggest that the alteration of miR-16 expression in decidua-derived mesenchymal stem cells may be involved in the development of pre-eclampsia.
Immunology and Reproductive Biology Laboratory, Medical School & State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, China.
Yaping
Y
Wang
Hongye
H
Fan
Guangfeng
G
Zhao
Dan
D
Liu
Leilei
L
Du
Zhiqun
Z
Wang
Yali
Y
Hu
Yayi
Y
Hou
D016022:Case-Control Studies; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000473:pathology*; D035683:MicroRNAs / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D011225:Pre-Eclampsia / Q000473:pathology*; D011247:Pregnancy; D060888:Real-Time Polymerase Chain Reaction; D012720:Severity of Illness Index; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
C505362:MIRN16 microRNA, human; D035683:MicroRNAs; D042461:Vascular Endothelial Growth Factor A