Genomic expression profiles of blood and placenta reveal significant immune‐related pathways and categories in Chinese women with gestational diabetes mellitus

Zhao, Yin; Wang, D.-P.; Zhang, L.-L.; Zhang, F.; Zhang, W.-Y.

doi:10.1111/j.1464-5491.2010.03140.x

Cited by 49 publications

(48 citation statements)

References 38 publications

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“…The mechanisms linking excess adiposity to an elevated risk of GDM are not completely understood, but recent evidence points to the role of specific hormones and cytokines known as adipokines, which are secreted by the adipose tissue [36,37]. In addition, transcriptome signatures obtained from placenta [38] and whole blood cells [39] have identified genes involved with lipid metabolism that are differentially expressed between T1D and GDM. Recently, in a meta-analysis of the transcription profiles of T1D, T2D and GDM patients, our group reported that gene expression signatures of GDM patients were closer to those of T1D patients than to T2D [40].…”

Section: Introductionmentioning

confidence: 99%

Integrative analysis of the transcriptome profiles observed in type 1, type 2 and gestational diabetes mellitus reveals the role of inflammation

et al. 2014

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BackgroundType 1 diabetes (T1D) is an autoimmune disease, while type 2 (T2D) and gestational diabetes (GDM) are considered metabolic disturbances. In a previous study evaluating the transcript profiling of peripheral mononuclear blood cells obtained from T1D, T2D and GDM patients we showed that the gene profile of T1D patients was closer to GDM than to T2D. To understand the influence of demographical, clinical, laboratory, pathogenetic and treatment features on the diabetes transcript profiling, we performed an analysis integrating these features with the gene expression profiles of the annotated genes included in databases containing information regarding GWAS and immune cell expression signatures.MethodsSamples from 56 (19 T1D, 20 T2D, and 17 GDM) patients were hybridized to whole genome one-color Agilent 4x44k microarrays. Non-informative genes were filtered by partitioning, and differentially expressed genes were obtained by rank product analysis. Functional analyses were carried out using the DAVID database, and module maps were constructed using the Genomica tool.ResultsThe functional analyses were able to discriminate between T1D and GDM patients based on genes involved in inflammation. Module maps of differentially expressed genes revealed that modulated genes: i) exhibited transcription profiles typical of macrophage and dendritic cells; ii) had been previously associated with diabetic complications by association and by meta-analysis studies, and iii) were influenced by disease duration, obesity, number of gestations, glucose serum levels and the use of medications, such as metformin.ConclusionThis is the first module map study to show the influence of epidemiological, clinical, laboratory, immunopathogenic and treatment features on the transcription profiles of T1D, T2D and GDM patients.

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Section: Introductionmentioning

confidence: 99%

Integrative analysis of the transcriptome profiles observed in type 1, type 2 and gestational diabetes mellitus reveals the role of inflammation

et al. 2014

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“…Roles include nutrient supply to the fetus, removal from the fetus of metabolic waste and hormone production. Placental phenotypes for intrauterine growth restriction (McCarthy et al 2007, Struwe et al 2010, pre-eclampsia (Hass et al 2006, Dexlin-Mellby et al 2010 and diabetes in pregnancy (Radaelli et al 2003, Zhao et al 2011 have been described, but these have not specifically been studied in the context of maternal obesity. However, animal models have been crucial in delineating the impact of obesity on placental function.…”

Section: Introductionmentioning

confidence: 99%

The effect of pre-existing maternal obesity on the placental proteome: two-dimensional difference gel electrophoresis coupled with mass spectrometry

Oliva¹,

Barker²,

Riley³

et al. 2012

Journal of Molecular Endocrinology

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Our aim was to study the protein expression profiles of placenta obtained from lean and obese pregnant women with normal glucose tolerance at the time of term Caesarean section. We used two-dimensional difference gel electrophoresis (2D-DIGE), utilising narrow-range immobilised pH gradient strips that encompassed the broad pH range of 4–5 and 5–6, followed by MALDI-TOF mass spectrometry of selected protein spots. Western blot and quantitative RT-PCR (qRT-PCR) analyses were performed to validate representative findings from the 2D-DIGE analysis. Eight proteins were altered (six down-regulated and two up-regulated on obese placentas). Annexin A5 (ANXA5), ATP synthase subunit beta, mitochondria (ATPB), brain acid soluble protein 1 (BASP1), ferritin light chain (FTL), heterogeneous nuclear ribonucleoprotein C (HNRPC) and vimentin (VIME) were all lower in obese patients. Alpha-1-antitrypsin (A1AT) and stress-70 protein, mitochondrial (GRP75) were higher in obese patients. Western blot analysis of ANXA5, ATPB, FTL, VIME, A1AT and GRP75 confirmed the findings from the 2D-DIGE analysis. For brain acid soluble protein 1 and HNRPC, qRT-PCR analysis also confirmed the findings from the 2D-DIGE analysis. Immunohistochemical analysis was also used to determine the localisation of the proteins in human placenta. In conclusion, proteomic analysis of placenta reveals differential expression of several proteins in patients with pre-existing obesity. These proteins are implicated in a variety of cellular functions such as regulation of growth, cytoskeletal structure, oxidative stress, inflammation, coagulation and apoptosis. These disturbances may have significant implications for fetal growth and development.

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“…6,7 Additionally, recent performed placental and blood transcriptome analysis in diabetic Chinese patients has shown GDM-dependent alterations in the expression of numerous immune-related genes, supporting the hypothesis of a linkage of immune system to GDM. 8 Among a panel of known immune-related genes, inducible nitric oxide (NO) synthase (iNOS), also termed as NOS2, and surfactant protein D (SP-D), a collagenous calcium-dependent lectin (or collectin), have drawn much attention as molecules not only related to inflammation but also with glucose and lipid metabolism.…”

Section: Introductionmentioning

confidence: 99%

Increased expression of immune-related genes in leukocytes of patients with diagnosed gestational diabetes mellitus (GDM)

Wójcik

Zieleniak

Źurawska-Kliś

et al. 2015

Exp Biol Med (Maywood)

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Compelling evidence indicates that the immune system is linked to metabolism in gestational diabetes mellitus (GDM), but factors participating in these processes still are awaiting identification. Inducible nitric oxide synthase, encoded by the NOS2 gene, and surfactant protein D, encoded by the SFTPD gene, have been implicated in diabetes. We investigated NOS2 and SFTPD mRNA levels in leukocytes obtained from 125 pregnant women with (n ¼ 87) or without (control group; n ¼ 38) GDM, and, in turn, correlated their expression with clinical parameters of subjects. Leukocytes were isolated from the blood of pregnant women and NOS2 and SFTPD expression in these cells was determined by quantitative real time PCR (qRT-PCR). Univariate correlation analyses were performed to assess an association between leukocyte NOS2 and SFTPD expression and clinical characteristics of patients. qRT-PCR experiments disclosed significantly increased leukocyte NOS2 and SFTPD mRNA levels in hyperglycemic GDM patients (P < 0.05). In the entire study group, there were significant positive associations of leukocyte NOS2 and SFTPD mRNAs with C-reactive protein. Additionally, transcript level of SFTPD also correlated positively with fasting glycemia and insulin resistance. This study demonstrates that an impaired glucose metabolism in GDM may be predominant predictor of leukocyte NOS2 and SFTPD overexpression in diabetic patients. Furthermore, alterations in the expression of these genes are associated with glucose metabolism dysfunction and/or inflammation during pregnancy. In addition, these findings support the utilization of leukocytes as good experimental model to study a relationship between immune-related genes and metabolic changes in women with GDM, as well as to assess the potential mechanisms underlying these alterations.

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Genomic expression profiles of blood and placenta reveal significant immune‐related pathways and categories in Chinese women with gestational diabetes mellitus

Abstract: These newly identified key genes and pathways may provide valuable information about the pathogenesis of GDM and can be used to improve early diagnosis, prevention, medication design and clinical treatment.

Cited by 49 publications

References 38 publications

Integrative analysis of the transcriptome profiles observed in type 1, type 2 and gestational diabetes mellitus reveals the role of inflammation

Integrative analysis of the transcriptome profiles observed in type 1, type 2 and gestational diabetes mellitus reveals the role of inflammation

The effect of pre-existing maternal obesity on the placental proteome: two-dimensional difference gel electrophoresis coupled with mass spectrometry

Increased expression of immune-related genes in leukocytes of patients with diagnosed gestational diabetes mellitus (GDM)

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