Diagnostic value of dysregulated microribonucleic acids in the placenta and circulating exosomes in gestational diabetes mellitus

Abstract Aims/Introduction Differentially expressed microribonucleic acids (miRNAs) in the placenta and circulating exosomes are of diagnostic value for gestational diabetes mellitus (GDM). In a cross‐sectional study, we identified miRNAs expressed both in the placenta and circulating exosomes of pr...

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Main Authors: Lei Zhang, Ting Zhang, Daoxu Sun, Guanghui Cheng, Hanxiao Ren, Haijie Hong, Liyu Chen, Xue Jiao, Yijia Du, Yuqing Zou, Lina Wang
Format: Article
Language:English
Published: Wiley 2021-08-01
Series:Journal of Diabetes Investigation
Subjects:
Online Access:https://doi.org/10.1111/jdi.13493
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author Lei Zhang
Ting Zhang
Daoxu Sun
Guanghui Cheng
Hanxiao Ren
Haijie Hong
Liyu Chen
Xue Jiao
Yijia Du
Yuqing Zou
Lina Wang
author_facet Lei Zhang
Ting Zhang
Daoxu Sun
Guanghui Cheng
Hanxiao Ren
Haijie Hong
Liyu Chen
Xue Jiao
Yijia Du
Yuqing Zou
Lina Wang
author_sort Lei Zhang
collection DOAJ
description Abstract Aims/Introduction Differentially expressed microribonucleic acids (miRNAs) in the placenta and circulating exosomes are of diagnostic value for gestational diabetes mellitus (GDM). In a cross‐sectional study, we identified miRNAs expressed both in the placenta and circulating exosomes of pregnant women with GDM, and estimated their diagnostic value. Materials and Methods Next‐generation sequencing was used to identify miRNAs in the placenta that were differentially expressed between GDM and normal glucose tolerance pregnancies. Quantitative polymerase chain reaction was used to validate the identified targets. Western blot and transmission electron microscopy were used to validate exosomes. Univariate logistic regression analysis was used to establish diagnostic models based on miRNAs expression, and the diagnostic value was estimated using the receiver operator characteristic curve. Results We identified 157 dysregulated miRNAs in the placental tissue obtained from GDM pregnancies. Of these, miRNA‐125b was downregulated (P < 0.001), whereas miRNA‐144 was upregulated (P < 0.001). The patterns of these two miRNAs remained the same in circulating exosomes from GDM pregnancies (all P < 0.001). miRNA‐144 levels in the circulating exosomes negatively correlated with body mass index both before pregnancy (P = 0.018) and before delivery (P = 0.039), and positively correlated with blood glucose at 1 h, estimated using the oral glucose tolerance test (P = 0.044). The area under curve for the established diagnostic model was 0.898, which was higher than blood glucose levels at 0 h. Conclusions These findings suggest that miRNA‐125b and miRNA‐144 are consistently dysregulated in circulating exosomes and the placenta from GDM pregnancies, and are of excellent diagnostic value for GDM.
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spelling doaj.art-cd9299312fe14e8b8a150e8884d547702022-12-21T20:15:51ZengWileyJournal of Diabetes Investigation2040-11162040-11242021-08-011281490150010.1111/jdi.13493Diagnostic value of dysregulated microribonucleic acids in the placenta and circulating exosomes in gestational diabetes mellitusLei Zhang0Ting Zhang1Daoxu Sun2Guanghui Cheng3Hanxiao Ren4Haijie Hong5Liyu Chen6Xue Jiao7Yijia Du8Yuqing Zou9Lina Wang10Department of Obstetrics The Second HospitalCheeloo College of MedicineShandong University Ji’nan ChinaDepartment of Pharmacy Jinan Infectious Disease HospitalCheeloo College of MedicineShandong University Ji’nan ChinaOffice of Heze Health Association Heze ChinaCentral Research Laboratory The Second HospitalCheeloo College of MedicineShandong University Ji’nan ChinaDepartment of Clinical Laboratory Medicine The Second HospitalCheeloo College of MedicineShandong University Ji’nan ChinaDepartment of Obstetrics The Second HospitalCheeloo College of MedicineShandong University Ji’nan ChinaDepartment of Obstetrics The Second HospitalCheeloo College of MedicineShandong University Ji’nan ChinaSchool of Medicine Cheeloo College of MedicineShandong University Ji’nan ChinaSchool of Medicine Cheeloo College of MedicineShandong University Ji’nan ChinaSchool of Medicine Cheeloo College of MedicineShandong University Ji’nan ChinaDepartment of Clinical Laboratory Medicine The Second HospitalCheeloo College of MedicineShandong University Ji’nan ChinaAbstract Aims/Introduction Differentially expressed microribonucleic acids (miRNAs) in the placenta and circulating exosomes are of diagnostic value for gestational diabetes mellitus (GDM). In a cross‐sectional study, we identified miRNAs expressed both in the placenta and circulating exosomes of pregnant women with GDM, and estimated their diagnostic value. Materials and Methods Next‐generation sequencing was used to identify miRNAs in the placenta that were differentially expressed between GDM and normal glucose tolerance pregnancies. Quantitative polymerase chain reaction was used to validate the identified targets. Western blot and transmission electron microscopy were used to validate exosomes. Univariate logistic regression analysis was used to establish diagnostic models based on miRNAs expression, and the diagnostic value was estimated using the receiver operator characteristic curve. Results We identified 157 dysregulated miRNAs in the placental tissue obtained from GDM pregnancies. Of these, miRNA‐125b was downregulated (P < 0.001), whereas miRNA‐144 was upregulated (P < 0.001). The patterns of these two miRNAs remained the same in circulating exosomes from GDM pregnancies (all P < 0.001). miRNA‐144 levels in the circulating exosomes negatively correlated with body mass index both before pregnancy (P = 0.018) and before delivery (P = 0.039), and positively correlated with blood glucose at 1 h, estimated using the oral glucose tolerance test (P = 0.044). The area under curve for the established diagnostic model was 0.898, which was higher than blood glucose levels at 0 h. Conclusions These findings suggest that miRNA‐125b and miRNA‐144 are consistently dysregulated in circulating exosomes and the placenta from GDM pregnancies, and are of excellent diagnostic value for GDM.https://doi.org/10.1111/jdi.13493Diagnostic modelExosomeGestational diabetes mellitus
spellingShingle Lei Zhang
Ting Zhang
Daoxu Sun
Guanghui Cheng
Hanxiao Ren
Haijie Hong
Liyu Chen
Xue Jiao
Yijia Du
Yuqing Zou
Lina Wang
Diagnostic value of dysregulated microribonucleic acids in the placenta and circulating exosomes in gestational diabetes mellitus
Journal of Diabetes Investigation
Diagnostic model
Exosome
Gestational diabetes mellitus
title Diagnostic value of dysregulated microribonucleic acids in the placenta and circulating exosomes in gestational diabetes mellitus
title_full Diagnostic value of dysregulated microribonucleic acids in the placenta and circulating exosomes in gestational diabetes mellitus
title_fullStr Diagnostic value of dysregulated microribonucleic acids in the placenta and circulating exosomes in gestational diabetes mellitus
title_full_unstemmed Diagnostic value of dysregulated microribonucleic acids in the placenta and circulating exosomes in gestational diabetes mellitus
title_short Diagnostic value of dysregulated microribonucleic acids in the placenta and circulating exosomes in gestational diabetes mellitus
title_sort diagnostic value of dysregulated microribonucleic acids in the placenta and circulating exosomes in gestational diabetes mellitus
topic Diagnostic model
Exosome
Gestational diabetes mellitus
url https://doi.org/10.1111/jdi.13493
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