Circulating Organ-Specific MicroRNAs Serve as Biomarkers in Organ-Specific Diseases: Implications for Organ Allo- and Xeno-Transplantation

Zhou, Ming; Hara, Hidetaka; Dai, Yifan; Mou, Lisha; Cooper, D. K. C.; Wu, Changyou; Cai, Zhiming

doi:10.3390/ijms17081232

Cited by 45 publications

(40 citation statements)

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“…Many organs are predicted to secrete miRNAs into circulation [36], however, during pregnancy fetal tissues like the placenta are an additional source of miRNAs in maternal circulation [37]. Consequently, maternal plasma miRNAs have a dual origin and may therefore serve as composite biomarkers for both maternal and fetal health.…”

Section: Introductionmentioning

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: Introductionmentioning

confidence: 99%

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

et al. 2016

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“…This might be due to an active reuptake process and decreased passive release of miRs by better functioning and less injured grafts. However, to confirm this hypothesis further research is warranted . Histological examination of the declined livers and comparing these data with HDmiR‐122 and CDmiR‐222 revealed a clear correlation with levels in perfusate prior, and, to a lesser extent, after NMP.…”

Section: Discussionmentioning

confidence: 84%

Cell‐free microRNAs as early predictors of graft viability during ex vivo normothermic machine perfusion of human donor livers

Matton

Selten

Roest

et al. 2020

Clinical Transplantation

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Background Cell‐free microRNAs (miRs) have emerged as early and sensitive biomarkers for tissue injury and function. This study aimed to investigate whether the release of hepatocyte‐derived microRNAs (HDmiRs) and cholangiocyte‐derived miRs (CDmiRs) correlates with hepato‐cholangiocellular injury and function during oxygenated, normothermic machine perfusion (NMP) of human liver grafts. Methods Donor livers (n = 12), declined for transplantation, were subjected to oxygenated NMP (6 hours) after a period of static cold storage (median 544 minutes (IQR 421‐674)). Perfusate and bile samples were analyzed by qRT‐PCR for HDmiR‐122 and CDmiR‐222. Spearman correlations were performed between miR levels and currently available indicators and classic markers. Results Both HDmiR‐122 and CDmiR‐222 levels in perfusate at 30 minutes of NMP strongly correlated with hepatocyte injury (peak perfusate AST) and cholangiocyte injury (peak biliary LDH). In bile, only CDmiR‐222 correlated with these injury markers. For hepato‐cholangiocellular function, both miRs in perfusate correlated with total bilirubin, while HDmiR‐122 (in perfusate) and CDmiR‐222 (in bile) correlated with bicarbonate secretion. Both the relative ratio of HDmiR‐122/CDmiR‐222 and AST in perfusate at 30 minutes significantly correlated with cumulative bile production, but only the relative ratio was predictive of histopathological injury after 6 hours NMP. Conclusion Early levels of HDmiR‐122 and CDmiR‐222, in perfusate and/or bile, are predictive of excretory functions and hepato‐cholangiocellular injury after 6 hours NMP. These miRs may represent new biomarkers for graft viability and function during machine perfusion.

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“…Предпо-лагается, что она также может оказывать влияние на инфильтрацию тканей иммунными клетками. Показано, что miR-92 воздействует на трансмем-бранные клеточные рецепторы integrin α5 и сфин-гозин-1-фосфат (S1P1), митоген-активированную протеинкиназу 4 (MKK4), играющую важную роль в активации Т-клеток, и эндотелиальную синтетазу оксида азота (eNOS), потенциально участвуя в ре-гуляции сосудистого компонента воспалительной реакции [42,43].…”

Section: микрорнк при остром клеточном отторжении трансплантированногunclassified

MicroRNAs in heart transplant recipients

Великий

Гичкун

Шевченко

2017

RJTAO

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1 ФГБУ «Федеральный научный центр трансплантологии и искусственных органов имени академика В.И. Шумакова» Минздрава России, Москва, Российская Федерация 2 ФГАОУ ВО «Первый Московский государственный медицинский университет имени И.М. Сеченова» Минздрава России (Сеченовский университет), Москва, Российская Федерация Представлен анализ данных, посвященных прогностической роли микроРНК при отторжении трансплан-тированного сердца. МикроРНК представляют собой класс малых некодирующих РНК, регулирующих экспрессию генов и влияющих на различные клеточные функции. Отмечены изменения их профилей при различных патологических процессах и отторжении солидных органов. Предположительно измерение уровней микроРНК при трансплантации сердца может иметь диагностическое и прогностическое значе-ние при оценке риска развития отторжения и возможности минимизации иммуносупрессивной терапии. В настоящее время клинических данных о роли этих биомаркеров при трансплантации сердца накоплено недостаточно, и необходимы дальнейшие исследования связи уровней микроРНК с различными клини-ческими и лабораторными показателями у реципиентов сердца.Ключевые слова: микроРНК, трансплантация сердца, отторжение, васкулопатия.

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Circulating Organ-Specific MicroRNAs Serve as Biomarkers in Organ-Specific Diseases: Implications for Organ Allo- and Xeno-Transplantation

Cited by 45 publications

References 147 publications

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

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

Cell‐free microRNAs as early predictors of graft viability during ex vivo normothermic machine perfusion of human donor livers

MicroRNAs in heart transplant recipients

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