title: Differential expression of microRNAs in decidua-derived mesenchymal stem cells from patients with pre-eclampsia.
abstract: BACKGROUND
  Mesenchymal stem cells (MSCs) at maternal-fetal interface are considered to play an important role in the pathogenesis of pre-eclampsia (PE). microRNAs (miRNAs) also have an important influence on differentiation, maturation, and functions of MSCs. Our aim in this study was to determine the differential expression of miRNAs in decidua-derived MSCs (dMSCs) from severe PE and normal pregnancies.
  
  
  RESULTS
  miRNA expression profiles in dMSCs from five patients with severe PE and five healthy pregnant women were screened using microarray. Then, bioinformatic analysis of the microarray results was performed. Out of 179 differentially expressed miRNAs, 49 miRNAs had significant (p < 0.05) differential expression of ≥ 2.0-fold changes, including 21 up-regulated and 28 down-regulated. miRNA-Gene-network and miRNA-Gene ontology (GO) -network analyses were performed. Overall, 21 up-regulated and 15 down-regulated miRNAs showed high degrees in these analyses. Moreover, the significantly enriched signaling pathways and GOs were identified. The analyses revealed that pathways associated with cell proliferation, angiogenesis, and immune functions were highly regulated by the differentially expressed miRNAs, including Wnt signaling pathway, mitogen-activated protein kinase signaling pathway, transforming growth factor beta signaling pathway, T-cell receptor signaling pathway, and B cell receptor signaling pathway. Four miRNA predicted target genes, vascular endothelial growth factor A (VEGFA), indoleamine 2,3-dioxygenase, suppression of cytokine signaling 3, and serine/threonine protein phosphatase 2A 55 kDa regulatory subunit B α isoform (PPP2R2A) were all decreased in dMSCs from patients with PE. Furthermore, the physiological roles of miR-16 and miR-136 in the down-regulation of VEGFA and PPP2R2A, respectively, were confirmed through reporter assays.
  
  
  CONCLUSIONS
  These findings suggest that miRNAs in dMSCs may be important regulatory molecules in the development of PE.
authors.forename: Guangfeng
authors.initials: G
authors.lastname: Zhao
authors.forename: Xue
authors.initials: X
authors.lastname: Zhou
authors.forename: Shiwen
authors.initials: S
authors.lastname: Chen
authors.forename: Huishuang
authors.initials: H
authors.lastname: Miao
authors.forename: Hongye
authors.initials: H
authors.lastname: Fan
authors.forename: Zhiqun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China. yali_hu@hotmail.com.
authors.forename: Yali
authors.initials: Y
authors.lastname: Hu
authors.forename: Yayi
authors.initials: Y
authors.lastname: Hou
mesh_terms: D000328:Adult; D049109:Cell Proliferation; D002478:Cells, Cultured; D003656:Decidua / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D020935:MAP Kinase Signaling System; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D035683:MicroRNAs / Q000096:biosynthesis*; D018919:Neovascularization, Physiologic; D011225:Pre-Eclampsia / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D015398:Signal Transduction; D060449:Wnt Signaling Pathway
chemical_list: D035683:MicroRNAs