scholarly journals Transcriptomics Analysis Reveals Shared Pathways in Peripheral Blood Mononuclear Cells and Brain Tissues of Patients With Schizophrenia

2021 ◽  
Vol 12 ◽  
Author(s):  
Xuemian Song ◽  
Yiyun Liu ◽  
Juncai Pu ◽  
Siwen Gui ◽  
Xiaogang Zhong ◽  
...  

Background: Schizophrenia is a serious mental disorder with complicated biological mechanisms. Few studies explore the transcriptional features that are shared in brain tissue and peripheral blood. In the present study, we aimed to explore the biological pathways with similar expression patterns in both peripheral blood mononuclear cells (PBMCs) and brain tissues.Methods: The present study used transcriptomics technology to detect mRNA expression of PBMCs of 10 drug-naïve patients with schizophrenia and 20 healthy controls. Transcriptome data sets of brain tissue of patients with schizophrenia downloaded from public databases were also analyzed in our study. The biological pathways with similar expression patterns in the PBMCs and brain tissues were uncovered by differential expression analysis, weighted gene co-expression network analysis (WGCNA), and pathway analysis. Finally, the expression levels of differential expressed genes (DEGs) were validated by real-time fluorescence quantitative polymerase chain reaction (qPCR) in another 12 drug-naïve patients with schizophrenia and 12 healthy controls.Results: We identified 542 DEGs, 51 DEGs, 732 DEGs, and 104 DEGs in PBMCs, dorsolateral prefrontal cortex, anterior cingulate gyrus, and nucleus accumbent, respectively. Five DEG clusters were recognized as having similar gene expression patterns in PBMCs and brain tissues by WGCNA. The pathway analysis illustrates that these DEG clusters are mainly enriched in several biological pathways that are related to phospholipid metabolism, ribosome signal transduction, and mitochondrial oxidative phosphorylation. The differential significance of PLAAT3, PLAAT4, PLD2, RPS29, RPL30, COX7C, COX7A2, NDUFAF2, and ATP5ME were confirmed by qPCR.Conclusions: This study finds that the pathways associated with phospholipid metabolism, ribosome signal transduction, and energy metabolism have similar expression patterns in PBMCs and brain tissues of patients with schizophrenia. Our results supply a novel insight for revealing the pathogenesis of schizophrenia and might offer a new approach to explore potential biological markers of peripheral blood in schizophrenia.

2012 ◽  
Vol 97 (6) ◽  
pp. E968-E972 ◽  
Author(s):  
Rongjiao Liu ◽  
Xinran Ma ◽  
Lingyan Xu ◽  
Dao Wang ◽  
Xiaohua Jiang ◽  
...  

Context: Graves' disease (GD) is a common autoimmune disease that affects the thyroid gland. As a new class of modulators of gene expression, microRNA (miRNA) have been reported to play a vital role in immune functions and in the development of autoimmunity and autoimmune disease. Objective: This study sought to characterize the different miRNA expression in peripheral blood mononuclear cells (PBMC) from GD patients and healthy individuals and examine their direct responses to T3 treatment. Methods: Forty-one patients who met criteria for initial GD, 13 GD patients in remission, and 35 healthy controls were recruited. Microarray was used to analyze the expression patterns of miRNA in PBMC obtained from initial GD patients and healthy controls. Three top-ranked miRNA were selected and validated by TaqMan-based real-time PCR in healthy controls, initial GD patients, and GD patients in remission. Furthermore, we cultured PBMC from healthy donors with or without T3 treatment to examine direct effects of T3 on selective miRNA. Results: There were sixteen miRNA expressed differently in PBMC from initial GD patients compared with normal subjects. Further analysis consistently showed that the expression of miR-154*, miR-376b, and miR-431* were suppressed in PBMC from initial GD patients. In addition, their expression levels were recovered in GD patients in remission. Meanwhile, T3 treatment could directly inhibit the expression of these miRNA in cultured PBMC from healthy subjects. Conclusions: The present work revealed that differentially expressed miRNA were associated with GD and T3 exposure, which might serve as novel biomarkers of GD and potential targets for GD treatment.


2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaoqian Fu ◽  
Guofu Zhang ◽  
Yansong Liu ◽  
Ling Zhang ◽  
Fuquan Zhang ◽  
...  

Abstract Background Schizophrenia is a severe, heritable, and refractory psychiatric disorder. Several studies have shown that the disrupted in schizophrenia 1 (DISC1) gene is closely associated with schizophrenia by its role in neuronal morphology, synaptic function, brain development, and dopamine homeostasis etc. This study intended to investigate the expression levels of DISC1 gene in schizophrenia patients compared with healthy controls, and the expression variation of DISC1 gene before and after antipsychotic treatment in schizophrenia patients. Methods In this study, we compared DISC1 expression levels in blood of 48 healthy controls, and 32 schizophrenia patients before and after 12 weeks of antipsychotic treatment using real-time quantitative PCR (RT-qPCR) analysis. Results The expression levels of DISC1 gene in peripheral blood mononuclear cells of schizophrenia patients before antipsychotic treatment were higher than those in healthy controls (P < 0.01); whereas after antipsychotic treatment, the expression levels of DISC1 gene in peripheral blood mononuclear cells of schizophrenia patients still remained increased (P < 0.01). Conclusions Our study provided further support for the involvement of DISC1 in the development of schizophrenia.


2011 ◽  
Vol 96 (11) ◽  
pp. E1866-E1870 ◽  
Author(s):  
Lingyan Xu ◽  
Xinran Ma ◽  
Yanyan Wang ◽  
Xiaoli Li ◽  
Yicheng Qi ◽  
...  

Abstract Context: Graves' disease (GD) is a common autoimmune disease that affects the thyroid gland. Its pathogenesis is tightly involved with aberrant proinflammatory cytokine production. Osteopontin (OPN), an extracellular matrix protein of pleiotropic properties, has recently been recognized as a potent inflammatory cytokine in several autoimmune diseases. Objective: This study sought to explore the pathophysiological role of OPN in GD by comparing OPN levels in initial GD patients and healthy controls. Methods: Seventy-six patients who met criteria for initial GD and sixty-five healthy controls were recruited. OPN and other clinical GD diagnosis parameters were measured. In addition, the coexpression of several OPN receptors as well as various nuclear factor-κB (NF-κB) downstream target genes were examined in peripheral blood mononuclear cells from human subjects. The effect of OPN on NF-κB activation was determined by in vitro assays. Results: We demonstrated for the first time that the OPN levels are enhanced in serum from GD patients. OPN levels are strongly associated with clinical serum parameters for GD diagnosis. The coexpression of selective OPN receptors and inflammatory response genes was enhanced in peripheral blood mononuclear cells from GD patients. Furthermore, serum from GD patients activated NF-κB activity in vitro, which was significantly suppressed by OPN monoclonal antibody abrogation. Conclusion: These data indicated a clinical correlation between serum OPN levels and GD. OPN could affect GD development through NF-κB activation and the subsequent changes in inflammatory milieu. OPN could serve as a novel biomarker for GD as well as a potential target for GD treatment.


1998 ◽  
Vol 5 (3) ◽  
pp. 362-368 ◽  
Author(s):  
Phillip Ruiz ◽  
Natalia Zacharievich ◽  
Mark Shenkin

ABSTRACT Dipeptidyl peptidase IV (DPP IV), also identified as the glycoprotein CD26, is a transmembrane 110- to 120-kDa serine aminopeptidase involved in immune responses by influencing T-cell costimulation and by cleaving cytokines. Additionally, CD26 is a nonintegrin receptor that contains a binding site for extracellular matrix and other molecules. In order to further define the expression and functional activity of this membrane exopeptidase in human T cells, we developed a nondisruptive, four-color cytofluorogenic assay that utilizes three separate antibodies to cell-surface molecules (e.g., CD4/CD8/CD26 and CD19/CD56/CD26) along with a rhodamine 110-conjugated dipeptide substrate that allows the measurement of DPP IV activity in phenotypically defined cells. We found normal human thymi to have notable differences in time-dependent DPP IV activity among the thymocyte subsets defined by their CD4/CD8 phenotype, with CD4−/CD8− thymocytes containing less DPP IV activity than cells expressing CD4 and/or CD8 (i.e., maturing). CD26 positivity was moderately intense in thymocytes and tended to identify cells with higher DPP IV activity. The four-color technique was also used to examine mature peripheral blood lymphocytes, along with an assortment of leukemias and transformed T-cell lines. These experiments revealed that while DPP IV was consistently evident in normal T cells, neoplastic T cells could vary in their expression patterns. Furthermore, the presence (or intensity) of surface CD26 in some abnormal T cells and certain normal peripheral blood mononuclear cells was separable from the level of DPP IV measured intracellularly. Our results established that multicolor cytofluorographic analysis can be a practical means to measure DPP IV activity in various human cell populations. Furthermore, we found that DPP IV activity could vary in T cells according to their differentiation status and that under certain circumstances surface CD26 expression can be disassociated from the level of measured enzyme (i.e., DPP IV) activity.


2014 ◽  
Vol 10 (9) ◽  
pp. 2398-2406 ◽  
Author(s):  
Mei-Ling Liu ◽  
Peng Zheng ◽  
Zhao Liu ◽  
Yi Xu ◽  
Jun Mu ◽  
...  

A GC-MS based metabolomic approach was applied to characterize the metabolic profiling of schizophrenia subjects (n = 69) and healthy controls (n = 85) in peripheral blood mononuclear cells (PBMCs) to identify and validate biomarkers for schizophrenia.


Author(s):  
Hiroshi Otsu ◽  
Mikio Watanabe ◽  
Naoya Inoue ◽  
Ryota Masutani ◽  
Yoshinori Iwatani

AbstractBackground:microRNAs (miRNAs) circulate in the blood and negatively regulate the expression of mRNAs. Some miRNAs are associated with the development of autoimmune thyroid diseases (AITD); however, there are few reports on the association between miRNA expression and the pathogenesis of AITD or the physiological variations of circulating miRNAs, which are important to examine as biomarkers.Methods:We examined the circadian and day-to-day variations in the expression levels of 5 miRNAs (miR-125a, miR-146a, miR-155, let-7e and miR-106a) in plasma and peripheral blood mononuclear cells (PBMC). We also analysed the expression levels of two of these miRNAs (miR-146a and miR-155) in 20 healthy controls, 60 Graves’ disease (GD) patients and 50 Hashimoto’s disease (HD) patients.Results:For each miRNA, we observed wide intraindividual variation [coefficient of variation value (CV): 70%–100%] compared to measurement error (CV: 20%–40%). In patients with AITD, HD, GD in remission and mild HD, the expression levels of miR-146a in PBMC were increased 296%, 328%, 348% and 464% above the levels in healthy controls, respectively (p=0.0443 and p=0.0273, p=0.0267 and p=0.0052, respectively). In severe HD, the expression level of miR-155 in plasma was increased to 347% of that in healthy controls (p=0.0256).Conclusions:The expression levels of miRNAs in plasma and PBMC showed wide intraindividual variation. In addition, miR-146a may be associated with the development of AITD.


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