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001-es BibID:BIBFORM065224
Első szerző:Lázár Levente (szülész-nőgyógyász)
Cím:Role of hsa-miR-325 in the etiopathology of preeclampsia / Levente Lázár, Bálint Nagy, Attila Molvarec, András Szarka, János Rigó
Dátum:2012
ISSN:1791-2997 1791-3004
Megjegyzések:Preeclampsia (PE) is a common pregnancy-specific syndrome characterized by hypertension and proteinuria. Evidence has demonstrated that hypertensive disorders in pregnancy are associated with alterations in the expression of different microRNAs (miRNAs). miRNAs are endogenously expressed non-coding RNAs that have significant biological and pathological functions due to their potential mechanisms of regulation of gene expression. The purpose of the present study was to investigate the expression of hsa-miR-325 in placental samples of preeclamptic and uncomplicated pregnancy patients. hsa-miR-325 was isolated from placenta tissue samples obtained from 31 preeclamptic and 28 normotensive pregnant females. Quantitative real-time polymerase chain reaction was used to analyze miRNA expression. The expression of hsa-miR?325 was elevated in uncomplicated pregnancies compared with preeclamptic patients. ?Ct (mean ? SD) values were 0.117?0.07 in PE tissues and 0.135?0.051 in normotensive cases (p<0.05). The expression levels correlated with patient blood pressure (p=0.015, r=-0.23), and tended to correlate with body mass index (p=0.065, r=0.261). The expression of hsa-miR-325 was downregulated in the case of PE. Changes in hsa-miR?325 expression in the case of pregnancy-related hypertensive disorders might affect the oxidative stress pathways and heat-shock protein production. These factors have a strong correlation with the development of PE. We, therefore, suggest that hsa-miR-325 contributes to the pathogenesis of PE.IntroductionHypertensive disorders are a leading cause of perinatal morbidity and mortality in pregnancy. Preeclampsia (PE) is a common pregnancy-specific syndrome that affects at least 5% of all pregnancies worldwide (1,2). It is characterized by hypertension (RR ?140/90 mmHg) and proteinuria of ?300 mg/24 h, developing after midgestation in previously normotensive pregnant females. Although the exact etiology of PE remains unknown, pathological studies have demonstrated the abnormal development of an ischemic placenta (2). Shallow endovascular trophoblast invasion in the spiral arteries and generalized endothelial cell dysfunction are key factors, while placental ischemia, oxidative stress and maternal-fetal immune maladaptation affect the development of PE. The only treatment is delivery of the placenta, after which the symptoms regress rapidly. Evidence has demonstrated that hypertensive disorders in non-pregnant and pregnant patients are associated with alterations in different miRNA expressions of specific tissues (3?5).miRNAs are non-protein coding RNAs, and functionally negative regulators of gene expression by antisense complementarity to specific messenger RNAs (6,7). They act by targeting the RNA-induced silencing complex to complementary sites within the 3·-untranslated region (UTR) of their target mRNAs. Depending on the degree of base pairing between the miRNA and the 3·-UTR, either degradation or translational repression of the targeted mRNA occurs. Although they account for less than 1% of all human genes, miRNAs have been estimated to regulate up to 30% of all protein-encoding genes (8). Their best-known representatives are the 18?24 nucleotide long single-stranded miRNA. The mean number of copies per cell is between 10 and 50000, depending on the tissue and the miRNA (9,10).Few studies have presented data regarding a comprehensive list of the human miRNAs expressed in the placenta and the possible roles of the different miRNAs in the pathophysiology of pregnancy-related disorders (11?13). Taking into consideration the high number of miRNAs, further studies regarding the expression of different miRNA in pregnancy-related hypertensive disorders may be important in understanding the pathophysiology of this disease.In the present study, we performed a real-time polymerase chain reaction PCR analysis of hsa-miR-325. hsa-miR-325 is located at Xq21.1. Different databases (http://www.mirdb.org; http://www.nextprot.org) were evaluated, and hsa-miR-325 was selected as it is a non-studied miRNA that targets genes and candidate protein regulatory pathways affecting different etiological factors, including body mass index (BMI), blood pressure regulation, oxidative stress, endometrial function and heat-shock protein regulation, thus playing a key role in the development of hypertensive disorders in pregnancy.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
miRNA
Preeclampsia
gene expression
Megjelenés:Molecular Medicine Reports 6 (2012), p. 597-600. -
További szerzők:Nagy Bálint (1956-) (molekuláris genetikus) Molvarec Attila (szülész-nőgyógyász) Szarka András Rigó János (1958-) (szülész-nőgyógyász)
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