@article{MTMT:30401681,
	title = {Circulating exosomal and Argonaute-bound microRNAs in preeclampsia},
	url = {https://m2.mtmt.hu/api/publication/30401681},
	author = {Biró, Orsolya and Fóthi, Ábel and Alasztics, Bálint and Nagy, Bálint and Orbán, Tamás I. and Rigó, János},
	doi = {10.1016/j.gene.2019.01.012},
	journal-iso = {GENE},
	journal = {GENE},
	volume = {692},
	unique-id = {30401681},
	issn = {0378-1119},
	abstract = {Introduction
		microRNAs (miRNAs) play important role in the regulation of placental development, and abnormal miRNA expression is associated with preeclampsia (PE). miRNAs are released from trophoblast cells to maternal blood flow, where they are highly stable, being encapsulated inside extracellular vesicles, like exosomes or bound to Argonaute proteins. In PE, placental dysfunction leads to aberrant extracellular miRNA secretion. hsa-miR-210 is a hypoxia-sensitive miRNA found to be upregulated in PE; however, it is unknown whether it is the cause or the consequence of the disease.
		
		Objective
		Our aim was to analyze the expression of several miRNAs, including hsa-miR-210 in placenta, exosome and Ago-bound fractions comparing normal (N) and PE pregnancies. We performed in vitro analyses of extracellular hsa-miR-210 secretion of trophoblast cell cultures (of villous and extravillous origin) under hypoxic condition.
		
		Methods
		PE and N placenta samples were collected from C-sections, and blood samples were drawn from each pregnant woman in the third trimester. HTR-8 and JAR cell lines were cultured in exosome-free media and treated with hypoxia-mimetic agents. Exosome and Ago-bound fractions were isolated by membrane affinity spin column method from plasma and cell media. Short RNAs were extracted from exosomes and vesicle-free fractions, and total-RNA was isolated from the placenta samples. The RNA purity and concentration were measured by spectrophotometry. Expression analysis was carried out by qPCR with specific primers to target and reference miRNAs.
		
		Results
		The level of hsa-miR-210 was significantly higher in PE placentas, which could cause a minor increase of exosomal and a high elevation of Ago-bound miR-210 in circulation. Hypoxia lead to intracellular hsa-miR-210 upregulation in trophoblast cell lines. In extravillous cell (HTR-8) media, only the level of exosomal hsa-miR-210 was increased but no change in Ago-bound hsa-miR-210 level was observed. In contrast, in villous cell (JAR) media, the level of exosomal hsa-miR-210 was increased and enhanced release of Ago-bound hsa-miR-210 was also observed.
		
		Conclusion
		Based on our data, we postulate that in PE, exosomal hsa-miR-210 is secreted actively from the trophoblast, and by intercellular communication, it may have a role in disease etiology. In addition, there is a passive release of Ago-bound hsa-miR-210 into the circulation, which may represent by-products of cell-death and is thereby a possible consequence of the disease.},
	year = {2019},
	eissn = {1879-0038},
	pages = {138-144},
	orcid-numbers = {Biró, Orsolya/0000-0002-4300-3602; Alasztics, Bálint/0000-0002-4011-8439; Nagy, Bálint/0000-0002-0295-185X; Orbán, Tamás I./0000-0002-3424-3428; Rigó, János/0000-0003-2762-6516}
}

@article{MTMT:3273020,
	title = {Various levels of circulating exosomal total-miRNA and miR-210 hypoxamiR in different forms of pregnancy hypertension},
	url = {https://m2.mtmt.hu/api/publication/3273020},
	author = {Biró, Orsolya and Alasztics, Bálint and Molvarec, Attila and Joó, József Gábor and Nagy, Bálint and Rigó, János},
	doi = {10.1016/j.preghy.2017.09.002},
	journal-iso = {PREGNANCY HYPERTENS},
	journal = {PREGNANCY HYPERTENSION},
	volume = {10},
	unique-id = {3273020},
	issn = {2210-7789},
	abstract = {Introduction: Hypertension is a common complication during pregnancy, affecting 10% of pregnant women worldwide. Several microRNA (miRNA) were shown to be involved in hypertensive disorders of pregnancy. In preeclampsia (PE), placental dysfunction causes the enhanced release of extracellular vesicle-derived miRNAs. The hypoxia-sensitive hsa-mir-210 is the most common PE-associated miRNA, but its exosomal profile has not been investigated. Objectives: Our aims were to measure exosomal total-miRNA concentration and to perform expression analysis of circulating exosomal hsa-miR-210 in women affected by chronic hypertension (CHT) gestational hypertension (GHT) or PE. Materials and methods: We collected plasma samples from women with CHT, GHT, PE (moderate: mPE and severe: sPE) and from normotensive pregnancies. Exosomal miRNAs were extracted and miRNA concentration was measured. RT-PCR was carried out with hsa-miR-210-3p-specific primers and relative expression was calculated using the comparative Ct method. Results: The total-miRNA concentration was different in the disease subgroups, and was significantly higher in mPE and sPE compared to the other groups. We found a significant difference in the relative exosomal hsa-miR-210-3p expression between all hypertensive groups compared to the normotensive samples, but significant upregulation was only observed in case of mPE and sPE patients. Both the level of total-miRNA and hsa-miR-210 expression was higher in case of severe PE. Conclusions: The level of circulating exosomal total-miRNA and hsa-miR-210 was elevated in women with PE, and it was higher in the severe form. We showed that hsa-miR-210 is secreted via exosomes, which may have a role in the pathomechanism of the disease. © 2017 International Society for the Study of Hypertension in Pregnancy.},
	keywords = {PREECLAMPSIA; microRNA; exosome; Maternal circulation},
	year = {2017},
	eissn = {2210-7797},
	pages = {207-212},
	orcid-numbers = {Biró, Orsolya/0000-0002-4300-3602; Alasztics, Bálint/0000-0002-4011-8439; Molvarec, Attila/0000-0002-3229-3034; Joó, József Gábor/0000-0001-9820-6514; Nagy, Bálint/0000-0002-0295-185X; Rigó, János/0000-0003-2762-6516}
}