Differential expression of microRNAs in decidua-derived mesenchymal stem cells from patients with pre-eclampsia

Abstract

BackgroundMesenchymal 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.ResultsmiRNA 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.ConclusionsThese findings suggest that miRNAs in dMSCs may be important regulatory molecules in the development of PE.

MiR-495 Promotes Senescence of Mesenchymal Stem Cells by Targeting Bmi-1

“…Our previous study showed that miR-495 was highly expressed in MSCs derived from decidua tissues of PE patients [31]. In the current study, we tested the expression of miR-495 in umbilical cord tissues and MSCs obtained from umbilical cords.…”

“…These findings suggest that abnormal MSCs may contribute to PE development. In our previous study, we found that miR-495 was one of the highly elevated miRNA in decidua-derived MSCs from PE patients [31]. Therefore, we speculated that miR-495 in MSCs may be involved in the pathogenesis of PE.…”

“…What’s more, miR-495 was reported to suppress breast cancer cell proliferation and tumorigenicity via G1-S arrest through targeting the 3’UTR of Bmi-1 [30]. In our previous study, we reported that miR-495 was highly expressed in MSCs [31]. But the role of miR-495 plays in senescence regulation hasn’t been reported yet.…”

The role of microRNAs in the proliferation, differentiation, invasion, and apoptosis of trophoblasts during the occurrence of preeclampsia—A systematic review

“…Studies have confirmed that expression of miR-29b is upregulated in placenta samples from severe preeclampsia patients [45,73] and in MSCs from the decidual tissue [37] from severe preeclampsia patients. Specifically, Li et al [45] found that increased expression of miR29b is able to inhibit the invasion of trophoblasts and decreased network formation and the number of capillary tubes.…”

“…In general, these studies have investigated the differential expression of miRNAs using several sources of experimental material, including placenta [33e36,38,40,47e51,54e57, 59e62,66,68,70e74], plasma [39,41e46,50,63e67], PBMCs [52], HUVECs [69], and MSCs from the decidua or the umbilical cord [37,53,58]; these samples were obtained from women who had preeclampsia and from women undergoing a normal pregnancy. These studies were carried out in The People's Republic of China [33e35, 37,40,42,43,45,50,52e58,63,64,67,69,72e74], the USA [32,46e48,51,54,61,70,71], South Korea [49], Canada [50,60], Japan [62], Turkey [65], Chile [66], Germany [68], Hungary [59], Switzerland [36], Norway [38], Italy [39], Spain [41], and the Czech Republic [44] (see Table 1 for details).…”