Human Exosomal Placenta-Associated miR-517a-3p Modulates the Expression of PRKG1 mRNA in Jurkat Cells1

Kambe, Saori; Yoshitake, Hiroshi; Yuge, Kazuya; Ishida, Yoichi; Ali, Md. Moksed; Takami, Takeshi; Kuwata, Tomoyuki; Ohkuchi, Akihide; Matsubara, Shigeki; Suzuki, Mitsuaki; Takeshita, Toshiyuki; Saito, Shigeru; Tajima, Toshihiro

doi:10.1095/biolreprod.114.121616

Cited by 79 publications

(65 citation statements)

References 46 publications

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“…The fetus may also contribute functional miRNAs to maternal circulation. For example, fetal cell-free RNA molecules appear in maternal plasma early during pregnancy and are maintained throughout pregnancy [73, 74], and trophoblast-secreted miRNAs have been shown to influence target gene expression in maternal immune cells [75]. Irrespective of their tissue source, the identified miRNAs are predicted to control important biological processes associated with fetal growth.…”

Section: Discussionmentioning

confidence: 99%

Plasma miRNA Profiles in Pregnant Women Predict Infant Outcomes following Prenatal Alcohol Exposure

et al. 2016

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Fetal alcohol spectrum disorders (FASD) are difficult to diagnose since many heavily exposed infants, at risk for intellectual disability, do not exhibit craniofacial dysmorphology or growth deficits. Consequently, there is a need for biomarkers that predict disability. In both animal models and human studies, alcohol exposure during pregnancy resulted in significant alterations in circulating microRNAs (miRNAs) in maternal blood. In the current study, we asked if changes in plasma miRNAs in alcohol-exposed pregnant mothers, either alone or in conjunction with other clinical variables, could predict infant outcomes. Sixty-eight pregnant women at two perinatal care clinics in western Ukraine were recruited into the study. Detailed health and alcohol consumption histories, and 2nd and 3rd trimester blood samples were obtained. Birth cohort infants were assessed by a geneticist and classified as unexposed (UE), heavily prenatally exposed and affected (HEa) or heavily exposed but apparently unaffected (HEua). MiRNAs were assessed in plasma samples using qRT-PCR arrays. ANOVA models identified 11 miRNAs that were all significantly elevated in maternal plasma from the HEa group relative to HEua and UE groups. In a random forest analysis classification model, a combination of high variance miRNAs, smoking history and socioeconomic status classified membership in HEa and UE groups, with a misclassification rate of 13%. The RFA model also classified 17% of the HEua group as UE-like, whereas 83% were HEa-like, at least at one stage of pregnancy. Collectively our data indicate that maternal plasma miRNAs predict infant outcomes, and may be useful to classify difficult-to-diagnose FASD subpopulations.

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Section: Discussionmentioning

confidence: 99%

Plasma miRNA Profiles in Pregnant Women Predict Infant Outcomes following Prenatal Alcohol Exposure

et al. 2016

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“…Exosomes are characterized by their contents, which reflect the physiological status of the origin cell and can regulate the phenotype of the target cell (Kambe et al, 2014; Bátiz et al, 2015; Sheller et al, 2016; Willms et al, 2016). At term, oxidative stress and inflammation build up in the amniotic cavity, causing cellular senescence of the fetal membranes and subsequent release of signals of cellular damage (Menon, 2014; Behnia et al, 2015, 2016; Polettini et al, 2015; Menon et al, 2016b).…”

Section: Discussionmentioning

confidence: 99%

Feto-Maternal Trafficking of Exosomes in Murine Pregnancy Models

et al. 2016

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Timing and initiation of labor are well-orchestrated by signals communicated between the fetal and maternal compartments; however, how these signals are communicated is not completely understood. Fetal exosomes, intercellular signaling vesicles, may play a key role in the process. The objective of this study was to evaluate exosome trafficking in vivo from fetal to maternal compartments. Pregnant CD-1 mice were intra-amniotically injected on gestational day 16 and 17 with exosomes isolated from primary human amnion epithelial cells fluorescently labeled with the lipophilic dye 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR). All our analyses were performed on samples collected on Day 18. After 24 h, mice were imaged using Bruker MS FX PRO In vivo Imager and tissues were collected. In vivo imaging of mouse showed fluorescence in the uterus, on the exosome-injected side whereas the uterine tissues from the uninjected side and saline and dye alone injected animals remained negative. Histological analysis of placenta showed exosome migration from the fetal to the maternal side of the placenta. Fluorescence released from exosomes was seen in maternal blood samples as well as in maternal uterus and kidneys. This study demonstrates that exosomal cargo can be carried through systemic route from the fetal to the maternal side of the uterine tissues during pregnancy, supporting the idea that fetal signals can be delivered via exosomes.

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“…The exosomal transfer of placenta-specific miRNA (miR-571a-3p) into 2 cell lines (human Treg cells and a leukemic T-cell line, Jurkat) and repression of a target gene (PRKG1) has been reported. 14 Previous studies have established that miRNAs are involved in the pathogenesis of diabetes and are required for pancreatic development and the regulation of glucose-stimulated insulin secretion. 36 Moreover, differences in the expression of miRNA such as miR-146a, miR-21, miR-29a, miR-34a, miR-222, and miR-375 have been reported in pancreatic b-cells, liver, adipose tissue, and/or skeletal muscle of animal models of type 1 or type 2 diabetes.…”

Section: Ajogorgmentioning

confidence: 99%