scholarly journals The association between expression of lncRNAs in patients with GDM

2021 ◽  
Author(s):  
Li Yuanyuan ◽  
Li Dongmei ◽  
Cheng Xingbo

Objective: Gestational diabetes mellitus (GDM) is common worldwide and seriously threatens maternal and infant health. The expression of non-coding RNA is tissue-specific and highly stable in eukaryotic cells and the circulatory system, which can act as an early molecular marker of GDM. Methods: The differential expression of lncRNA and mRNA in the peripheral blood of patients with GDM (experimental group) and healthy pregnant women (control group) was analysed via lncRNA gene chip. Employing biological function clustering and KEGG signal pathway analysis, we selected the mRNAs and lncRNAs closely related to the insulin signal pathway of GDM to analys the possible regulatory mechanism in the pathogenesis of GDM. The sequencing results were further verified via quantitative polymerase chain reaction (Q-PCR). Results: lncRNA microarray analysis revealed 7498 genes (3592 upregulated, 3906 downregulated) differentially expressed in the GDM group and healthy pregnant women control group, including 1098 differentially expressed lncRNAs (609 upregulated, 489 downregulated). According to the regulatory pathway of lncRNA mRNA network,six lncRNAs and four mRNAs were found to play a significant role in insulin resistance. Conclusions: The lncRNAs ERMP1,TSPAN32 and MRPL38 form a co-expression network with TPH1, which is mainly involved in the tryptophan metabolism pathway and in the development of GDM, Moreover, lncRNA RPL13P5 forms a co-expression network with the TSC2 gene via the pi3k-akt and insulin signalling pathways, which are involved in the process of insulin resistance in GDM.

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1003
Author(s):  
Margarita L. Martinez-Fierro ◽  
Idalia Garza-Veloz

microRNAs are important regulators of cell processes and have been proposed as potential preeclampsia biomarkers. We evaluated serum microRNA expression profiling to identify microRNAs involved in preeclampsia development. Serum microRNA expression profiling was evaluated at 12, 16, and 20 weeks of gestation (WG), and at the time of preeclampsia diagnosis. Two groups were evaluated using TaqMan low-density array plates: a control group with 18 normotensive pregnant women and a case group with 16 patients who developed preeclampsia during the follow-up period. Fifty-three circulating microRNAs were differentially expressed between groups (p < 0.05). Compared with controls, hsa-miR-628-3p showed the highest relative quantity values (at 12 WG = 7.7 and at 20 WG = 3.45) and the hsa-miRs -151a-3p and -573 remained differentially expressed from 16 to 20 WG (p < 0.05). Signaling pathways including cancer-related, axon guidance, Neurotrophin, GnRH, VEGF, and B/T cell receptor, were most commonly altered. Further target gene prediction revealed that nuclear factor of activated T-cells 5 gene was included among the transcriptional targets of preeclampsia-modulated microRNAs. Specific microRNAs including hsa-miRs -628-3p, -151a-3p, and -573 were differentially expressed in serum of pregnant women before they developed preeclampsia compared with controls and their participation in the preeclampsia development should be considered.


2021 ◽  
Vol 17 (4) ◽  
pp. 346-356
Author(s):  
I. S. Lipatov ◽  
Yu. V. Tezikov ◽  
A. R. Azamatov

Background: An in-depth study of dismetabolic mechanisms in the genesis of pre-eclampsia (PE) has been updated because pregnancy is considered as a natural model of metabolic syndrome (MS), as well as the metabolic disorders are important in development of essential hypertension.Aims: to reveal clinical and laboratory parallels in pregnancy complicated by PE without MS and pregnancy proceeding on the background of MS to assess the role of metabolic disturbances in the development of PE.Materials and methods: 82 women with MS were examined in the dynamics of pregnancy and were divided into 2 groups depending on the implementation of PE: group I consisted of 50 women with PE on the background of MS, group II 32 women with MS without PE. We formed group III consisting of 44 pregnant women with PE without accompanying diseases to assess the pathogenetic value of metabolic disorders in the development of PE. The IV (control) group consisted of 30 healthy women with physiological pregnancy. Metabolic, hematological parameters, hormones, markers of the proinflammatory state, endothelial hemostasiological dysfunction, decidualization and placental angiogenesis, accumulation dynamics and distribution loci of adipose tissue were determined in all pregnant women.Results: In the groups of pregnant women with PE, changes similar to MS were revealed: pronounced diabetic and atherogenic disorders with the development of pathological insulin resistance, hyperinsulinemia and leptinemia, endothelial-platelet link hyperactivation, thrombotic and inflammatory status, visceral type of fat deposition, hyperuricemia, hypersympathicotonia. It is proved that in the hierarchy of mechanisms of PE formation, placental dysfunction is a secondary alteration factor, which additionally potentiates the insulin resistance increase and the effects of structural and functional destabilization of the vascular endothelium.Conclusions: The direction of metabolic changes during pregnancy, the common development of PE and MS indicate the important role of dismetabolic mechanisms in the formation of PE.


2020 ◽  
Vol 5 (1) ◽  
pp. 45-55
Author(s):  
Shuwei Wan ◽  
Hui Cao ◽  
Yubo Zhao ◽  
Yaming Guo ◽  
Chuang Li ◽  
...  

Objective: Intimal hyperplasia is the main cause of restenosis of vein grafts after venous transplantation. MicroRNAs are considered to play a role in vein graft restenosis; however, the expression profile of microRNAs in neointima has not been reported in detail. We wanted to investigate the differentially expressed microRNAs in the restenosis of vein grafts in rats.Methods: We established a rat model for vein transplantation to explore the pathogenic roles of microRNAs during intimal hyperplasia. Hematoxylin and eosin staining was used to confirm intimal hyperplasia in the vein grafts. Changes in microRNA expression in the vein grafts were detected 3 and 14 days after surgery by sequencing, reverse transcription‐quantitative polymerase chain reaction, and bioinformatics analyses for functional annotation.Results: We detected 711 newly predicted microRNAs among all the comparisons. Among these comparisons, 437 differentially expressed microRNAs were detected in the postoperative day 3 group versus the control group, 265 were detected in the postoperative day 14 group versus the control group, and 158 were detected in the postoperative day 14 group versus the postoperative day 3 group. Pathway analysis revealed significant enrichment of target genes that mediate Wnt, mitogen-activated protein kinase, vascular smooth muscle contraction, and regulation of actin cytoskeleton signaling.Conclusion: Our results provide insight into the pathogenesis of restenosis and will help develop novel targets in the prevention and treatment of vein graft restenosis.


2021 ◽  
Vol 70 (4) ◽  
pp. 73-79
Author(s):  
Anna I. Malyshkina ◽  
Natalia Y. Sotnikova ◽  
Dmitriy N. Voronin ◽  
Alena V. Kust

BACKGROUND:The frequency of recurrent miscarriage is up to 5 % of all desired pregnancies and is mainly due to immunological disorders. Dysfunction in the regulation of the functional activity of B lymphocytes is the pathogenetic link in multiple obstetric complications, including habitual miscarriage. AIM:The aim of this study was to characterize the regulation of the functional activity of peripheral B lymphocytes in pregnant women with threatened spontaneous miscarriage and a history of habitual miscarriage. MATERIALS AND METHODS:We examined 88 women aged 18-40 years at a gestation period of 5-12 weeks. The main group consisted of 36 patients with threatened spontaneous miscarriage at the time of examination and a history of habitual miscarriage. The control group included 28 women with uncomplicated pregnancy. The comparison group consisted of 24 primary pregnant patients with threatened spontaneous abortion at the time of examination. BAFF and APRIL levels in the blood serum were determined by enzyme immunoassay. The content of CD19+BAFFR+B lymphocytes in the lymphocyte gate was evaluated in the peripheral blood by flow cytometry using monoclonal antibodies. Akt mRNA expression was assessed using real-time reverse-transcription quantitative polymerase chain reaction. CD19+В lymphocytes were isolated by direct magnetic separation. RESULTS:In the main group, there was an increase in expression of BAFF receptors on peripheral CD19+B lymphocytes and a decrease in the serum BAFF concentration compared to the parameters in the other study groups. We also found a pronounced trend towards a decrease in the serum APRIL level in the main and comparison groups of patients compared to healthy pregnant women. Besides, Akt mRNA expression in peripheral CD19+B lymphocytes was increased in the main group. CONCLUSIONS:Threatened habitual abortion is associated with the deficit of the regulatory influence of BAFF and APRIL, which is expressed in the disruption of B cell homeostasis and the weakening of humoral effector mechanisms.


2016 ◽  
Vol 62 (5) ◽  
pp. 31-32 ◽  
Author(s):  
Polina Popova ◽  
Aleksandra Tkachuk ◽  
Aleksandra Dronova ◽  
Yana Bolotko ◽  
Elena Grineva

Background and aims. Placental hormones and proteins are important regulators of insulin resistance during pregnancy. However, the data concerning the assosiation between placental lactogen (PL) and placental growth factor (PLGF) level in early pregnancy and further development of gestational diabetes mellitus (GDM) are limited and incostintent. The aim of this study was to compare the level of these two placental proteins and homeostasis model assessment of insulin resistance (HOMA-IR) in early pregnancy among women diagnosed with and without GDM months later.Materials and methods. A nested case-control study was conducted in a prospective cohort of pregnant women. Among them, 78 incident GDM cases were identified and 95 women who were not diagnosed with GDM were randomly selected as a control group. Blood was sampled for measurements of PL, PLGF, fasting plasma glucose and insulin at 8-14 weeks of pregnancy. All the women underwent oral glucose tolerance test (OGTT) at 24-32 weeks. GDM was diagnosed according to the International Association of Diabetes In Pregnancy Study Groups (IADPSG) recommendations (fasting glucose ≥5.1 mmol / l and / or 1 hour ≥10.0 mmol / l and / or 2 hours ≥8.5 mmol / L). The maternal and neonatal anthropometric parameters were also measured. Statistical analysis included Student's t-test, logistic regression and Pearson's correlation.Results. There was no difference between GDM and control groups in the mean levels of PL (0,70 +/- 0,53 vs 0,81 +/- 0,58 mg/L, р =0,215 ) and PLGF (60,7 +/- 169.6 vs 46,6+105,6 pg/ml, р=0,503). Women with GDM were older (30.2 +/- 3.9 vs 28.4 +/- 4.7 years, p = 0.008), had higher first trimester body mass index (BMI) (25.2 +/- 5.2 vs 23.1 +/- 4.6 kg/m2, р = 0.006), higher levels of insulin (10.3 +/- 5.5 vs 7.9 +/- 3.9 mU/L, p = 0,007) and HOMA-IR ( 2.17 +/- 1.1 vs 1.7 +/- 0.9, p = 0,007) compared to the control group. Women with GDM also had a higher level of fasting plasma glucose (4.8 + 0.6 and 4.6 + 0,5 mmol/L, p = 0.063), although the difference did not reach statistical significance. HOMA-IR was positively associated with the development of GDM (OR: 1.62, 95% CI: 1.12 - 2.34, P = 0.01) and the association retained under a multivariable analysis controlling for age and BMI (OR: 1.59, 95% CI: 1.04 - 2.45, P = 0.033). Maternal PL and PLGF were not related to the results of OGTT, HOMA-IR or neonatal anthropometry. A positive correlation between PL level and gestational age at the time of blood sampling was observed (r = 0.657, p <0.001).Conclusion. Serum concentrations of PL and PLGF in pregnant women at 8-14 weeks’ gestation were not associated with HOMA-IR and later development of GDM. Higher HOMA-IR score in early pregnancy is significantly associated with an elevated risk for GDM.


2002 ◽  
pp. 243-248 ◽  
Author(s):  
L Kalabay ◽  
K Cseh ◽  
A Pajor ◽  
E Baranyi ◽  
GM Csakany ◽  
...  

OBJECTIVE: Human fetuin/alpha(2)-HS-glycoprotein (AHSG) is a 49 kDa serum and tissue protein which is a natural inhibitor of insulin receptor signaling. We investigated serum AHSG levels during pregnancy and whether the protein is involved in insulin resistance observed in healthy pregnant women and patients with gestational diabetes. DESIGN: One hundred and four healthy pregnant women and 23 of their neonates, 30 patients with gestational diabetes and their neonates and 30 healthy age-matched non-pregnant females as a control group were investigated in a case-control cross-sectional study. METHODS: Serum AHSG was determined by radial immunodiffusion. RESULTS: We observed an increase of serum AHSG concentration in the second and third trimesters. Gestational diabetes patients had significantly higher AHSG levels than healthy pregnant women and non-pregnant controls. There was a highly significant positive correlation between serum AHSG concentration and indirect parameters of insulin resistance, i.e. tumor necrosis factor-alpha (TNF-alpha), leptin, C-peptide and C-peptide/blood glucose ratio. There was also a negative correlation between maternal AHSG, TNF-alpha, leptin levels and head circumference, body length and body weight of newborns. CONCLUSION: AHSG, TNF-alpha and leptin may contribute to insulin resistance during normal pregnancy and gestational diabetes. AHSG along with these cytokines may also negatively regulate neonatal skeletal development.


Author(s):  
Shengnan Cong ◽  
Jinlong Li ◽  
Jingjing Zhang ◽  
Jingyi Feng ◽  
Aixia Zhang ◽  
...  

Lubrication disorder is a common health issue that manifests as insufficient sexual arousal at the beginning of sex. It often causes physical and psychological distress. However, there are few studies on lubrication disorder, and the complexity of circular RNA (circRNA) and the related competing endogenous RNA (ceRNA) network in lubrication disorder is still poorly known. Therefore, this study aims to build a regulatory circRNA-micro (mi)RNA-mRNA network and explore potential molecular markers of lubrication disorder. In the study, 12 subjects were recruited, including 6 in the lubrication disorder group and 6 in the normal control group. RNA sequencing was exploited to identify the expression profiles of circRNA, miRNA and mRNA between two groups, and then to construct the circRNA-miRNA-mRNA networks. The enrichment analyses of the differentially expressed (DE)-mRNAs were examined via Gene Set Enrichment Analysis (GSEA). Furthermore, the expression level and interactions among circRNA, miRNA, and mRNA were validated using real-time quantitative polymerase chain reaction (RT-qPCR) and dual-luciferase reporter assays. In the results, 73 circRNAs, 287 miRNAs, and 354 target mRNAs were differentially expressed between two groups when taking | Log2 (fold change)| &gt; 1 and P-value &lt; 0.05 as criteria, and then the results of GSEA revealed that DE-mRNAs were linked with “vascular smooth muscle contraction,” “aldosterone regulated sodium reabsorption,” “calcium signaling pathway,” etc. 19 target relationships among 5 circRNAs, 4 miRNAs, and 7 mRNAs were found and constructed the ceRNA network. Among them, hsa-miR-212-5p and hsa-miR-874-3p were demonstrated to be related to the occurrence of lubrication disorder. Eventually, consistent with sequencing, RT-qPCR showed that hsa_circ_0026782 and ASB2 were upregulated while hsa-miR-874-3p was downregulated, and dual-luciferase reporter assays confirmed the interactions among them. In summary, the findings indicate that the circRNA-miRNA-mRNA regulatory network is presented in lubrication disorder, and ulteriorly provide a deeper understanding of the specific regulatory mechanism of lubrication disorder from the perspective of the circRNA-miRNA-mRNA network.


2018 ◽  
Vol 46 (6) ◽  
pp. 2576-2586 ◽  
Author(s):  
Min Jiang ◽  
Gendie E. Lash ◽  
Xueqing Zhao ◽  
Yan Long ◽  
Caijiao Guo ◽  
...  

Background/Aims: Circular RNAs (circRNAs) are transcribed prevalently in the genome; however, their potential roles in multiple cardiovascular diseases, particularly preeclampsia (PE), are not yet well understood. This study investigated the expression profiles of circRNAs and explored circRNA-mediated pregnancy-associated plasma protein A (PAPP-A) expression as a potential biomarker for PE before 20 weeks of pregnancy. Methods: A nested case-control two-phase screening/validation study was performed in pregnant women before 20 weeks of gestation (before clinical diagnosis) at Guangzhou Women and Children’s Medical Center from 2012 to 2015. In the screening phase, circRNA expression profiles of blood cells were assessed using a human circRNA microarray, which was designed to detect simultaneously 5396 circRNAs, in 5 patients with PE and 5 age- and gestational week-matched controls. In the validation phase, 18 circRNAs in blood cells predicted by bioinformatics tools were validated by quantitative reverse transcription PCR in a cohort of 60 patients (PE and age-, gestational week-, and sample storage time-matched controls). Then, we examined the involvement of circRNAs in PE-related pathways via interactions with miRNAs by multiple bioinformatics approaches. Bioinformatics analysis predicted that hsa_circ_0004904 and hsa_circ_0001855 miRNA sponges directly target PAPP-A. PAPP-A was verified in the serum of the same cohort of patients using an enzyme-linked immunosorbent assay. Finally, we combined PAPP-A with circRNAs to create a novel preclinical diagnostic model for PE with logistic regression and evaluated the efficiency of this model with receiver operating curve analysis. Results: Volcano plot analysis using various parameters showed that circRNAs were differentially expressed among both groups (P < 0.01, fold change > 2). In the screening phase, we found that 2178 circRNAs were differentially expressed between the control and PE groups, in which 884 circRNAs were downregulated and 1294 circRNAs were upregulated in the PE group compared with the control group. In the validation phase, two circRNAs, hsa_circ_0004904 and hsa_circ_0001855, were significantly upregulated in PE patients compared with healthy pregnant women (P < 0.05). PAPP-A expression levels, related to the two circRNAs based on bioinformatics prediction, were increased in the PE group compared with the control group. The area under the curve of the combined model was 0.94 in the predicted PE subjects. Conclusions: This is the first study to report circRNA profiling in patients with PE prior to the onset of symptoms. Our data suggested that hsa_circ_0004904 and hsa_circ_0001855 combined with PAPP-A might be promising biomarkers for the detection of PE. Moreover, circRNAs may provide new insights into the potential mechanisms underlying the pathophysiology of PE.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jingli Wang ◽  
Chengcheng Guan ◽  
Jing Sui ◽  
Yucui Zang ◽  
Yuwen Wu ◽  
...  

Abstract Background Xeroderma pigmentosum complementation group C (XPC) is a DNA damage recognition protein that plays an important role in nucleotide excision repair and can reduce oxidative stress, which may be involved in the development of preeclampsia (PE). Therefore, the aim of this study was to explore whether XPC polymorphisms were relevant to the genetic susceptibility to PE in Chinese Han women. Method A total of 1276 healthy pregnant women were included as the control group and 958 pregnant women with PE as the case group. DNA was extracted from peripheral blood samples to perform genotyping of loci rs2228001 and rs2228000 in XPC through real-time quantitative polymerase chain reaction (PCR). The relationship between XPC and susceptibility to PE was evaluated by comparing the genotypic and allelic frequencies between the two groups of pregnant women. Results Polymorphism of rs2228000 may be associated with PE risk and allele T may play a protective role (genotype, χ2 = 38.961, P < 0.001 and allele χ2 = 21.746 P < 0.001, odds ratio (OR) = 0.885, 95% confidence interval (CI) = 0.840-0.932). No significant difference was found between the two groups in rs2228001,(genotype χ2 = 3.148, P = 0.207 and allele χ2 = 0.59, P = 0.442, OR = 1.017, 95% CI = 0.974–1.062). When the frequencies of genotypes and alleles for early- and late-onset PE, mild PE and severe PE were compared with those of controls, the results were consistent with the large clinical sample. Conclusion Our data suggest that the genetic variant rs2228000 in XPC may be associated with PE risk in Chinese Han women, and that pregnant women with the TT genotype have a reduced risk of PE. Further investigations are needed to confirm these findings in other regions or larger prospective populations.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jingjing Li ◽  
Yajuan Xu ◽  
Zongzong Sun ◽  
Yanjun Cai ◽  
Biao Wang ◽  
...  

AbstractSubclinical hypothyroidism (SCH) has become a prevalent complication in pregnancy. Recent research links SCH to disturbed thyroid lipid profile; however, it is unclear how lipid metabolism disorders contribute to the pathogenesis of SCH during pregnancy. Thus, we used nontargeted lipidomics to identify and compare the lipids and metabolites expressed by pregnant women with SCH and healthy pregnant women. Multivariate analysis revealed 143 lipid molecules differentially expressed between the SCH group and the control group. Based on fold change, 30 differentially expressed lipid metabolites are potential biomarkers. KEGG pathway enrichment analysis showed that the differentially expressed metabolites participate in several pathways, including response to pathogenic Escherichia coli infection, regulation of lipolysis in adipocytes, metabolic pathways, glycerophospholipid metabolism, and fat digestion and absorption pathways. Correlation analyses revealed sphingomyelin (SM) and phosphatidylcholine (PC) positively correlate to tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and interleukin-6 (IL-6), while phosphatidylglycerol (PG), and phosphatidylinositol (PI) negatively correlate with them. In addition, PG positively correlates to birth weight. Thus, the lipid profile of pregnant women with SCH is significantly different from that of healthy pregnant women. Lipid molecules associated with the differential lipid metabolism, such as SM, phosphatidylethanolamine (PE), and PI, should be further investigated for their roles in the pathogenesis of SCH in pregnancy, as they might be targets for reducing the incidence of adverse pregnancy outcomes.


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