Gene expression profiles in peripheral blood mononuclear cells reflect the pathophysiology of type 2 diabetes

Takamura, Toshinari; Honda, Masao; Sakai, Yoshio; Ando, Hitoshi; Shimizu, Akiko; Ota, Tsuguhito; Sakurai, Masaru; Makino, Hírofumi; Kurita, Seiichiro; Nagata, Naoto; Uchikata, Masahiro; Nakamura, Seiji; Matoba, Ryo; Tanino, Motohiko; Matsubara, Kazuo

doi:10.1016/j.bbrc.2007.07.006

Cited by 73 publications

(63 citation statements)

References 18 publications

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“…We have analyzed gene expression in liver diseases (12,13) and believe it may become a useful diagnostic tool using liver tissue biopsy samples (14). We have also reported that gene expression profiling of PBMCs predicted the effect of IFN for the eradication of HCV (15) and can provide biomarkers not only for the control of blood sugar but also possibly for predisposing diabetic factors (16). Gene expression profiling of PBMCs from patients with renal cell carcinoma can be used to predict their response to systemic chemotherapy (17).…”

Section: Introductionmentioning

confidence: 99%

Common Transcriptional Signature of Tumor-Infiltrating Mononuclear Inflammatory Cells and Peripheral Blood Mononuclear Cells in Hepatocellular Carcinoma Patients

et al. 2008

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Hepatocellular carcinoma (HCC) is frequently associated with infiltrating mononuclear inflammatory cells. We performed laser capture microdissection of HCC-infiltrating and noncancerous liver-infiltrating mononuclear inflammatory cells in patients with chronic hepatitis C (CH-C) and examined gene expression profiles. HCC-infiltrating mononuclear inflammatory cells had an expression profile distinct from noncancerous liver-infiltrating mononuclear inflammatory cells; they differed with regard to genes involved in biological processes, such as antigen presentation, ubiquitin-proteasomal proteolysis, and responses to hypoxia and oxidative stress. Immunohistochemical analysis and gene expression databases suggested that the up-regulated genes involved macrophages and Th1 and Th2 CD4 cells. We next examined the gene expression profile of peripheral blood mononuclear cells (PBMC) obtained from CH-C patients with or without HCC. The expression profiles of PBMCs from patients with HCC differed significantly from those of patients without HCC (P < 0.0005). Many of the up-regulated genes in HCCinfiltrating mononuclear inflammatory cells were also differentially expressed by PBMCs of HCC patients. Analysis of the commonly up-regulated or down-regulated genes in HCCinfiltrating mononuclear inflammatory cells and PBMCs of HCC patients showed networks of nucleophosmin, SMAD3, and proliferating cell nuclear antigen that are involved with redox status, the cell cycle, and the proteasome system, along with immunologic genes, suggesting regulation of anticancer immunity. Thus, exploring the gene expression profile of PBMCs may be a surrogate approach for the assessment of local HCC-infiltrating mononuclear inflammatory cells.

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Section: Introductionmentioning

confidence: 99%

Common Transcriptional Signature of Tumor-Infiltrating Mononuclear Inflammatory Cells and Peripheral Blood Mononuclear Cells in Hepatocellular Carcinoma Patients

et al. 2008

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“…The blood of transplant recipients has also been profiled, in kidney [43], liver [44], heart [45], and hematopoeitic cell transplant recipients [46]. Furthermore, disease signatures have been detected in the blood of patients with diabetes [47,48], cardio vascular diseases [49], and nonhematological malignancies [50,51].…”

Section: Il-1b Mediated Diseases Resulting From Inflammasome Dysregulmentioning

confidence: 99%

Microarray-based identification of novel biomarkers in IL-1-mediated diseases

Allantaz

Chaussabel

Banchereau

et al. 2007

Current Opinion in Immunology

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SummaryInterleukin 1b (IL-1b) is emerging as mediator of a wide range of human diseases. Availability of IL-1 blockers that result in clinical benefits to patients with these diseases is creating a demand for biomarkers to diagnose as well as to predict and follow responses to therapy. Blood gene expression profiling can be used to identify such biomarkers. This review will summarize recent studies in the field and will discuss some of the challenges raised by the use of this technology in biomarker discovery.

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“…25) Takamura et al showed that c-Jun terminal kinase (JNK) and mitochondrial oxidative phosphorylation (OXPHOS) pathways of peripheral blood mononuclear cells (PBMCs) could be used as surrogate transcriptional markers in type 2 diabetes patients. 8) Liew et al showed that the peripheral blood transcriptome was a potential diagnostic tool and approximately 80% of genes expressed in any of nine human tissues were also found expressed in blood cells. 4) These results strongly suggest that blood gene expression provides useful information for whole-body analysis.…”

Section: Discussionmentioning

confidence: 99%

“…6,7) In addition, Takamura et al recently showed that gene expression in blood cells re-flected the pathophysiology of type 2 diabetes patients, supporting our hypothesis. 8) Thus, it is of great interest to identify genes that are differently expressed in both WBC and type 2 diabetes-related tissues, other than liver, before onset of disease.…”

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confidence: 99%

DNA Microarray Analysis of Whole Blood Cells and Insulin-Sensitive Tissues Reveals the Usefulness of Blood RNA Profiling as a Source of Markers for Predicting Type 2 Diabetes

Hayashi

Kajimoto

Iida

et al. 2010

Biological & Pharmaceutical Bulletin

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To determine if gene expression profiling of whole blood cells is a useful source of markers for the early diagnosis of the onset of type 2 diabetes, we examined gene expression profiling of whole blood cells and type 2 diabetes-related organs, such as liver, adipose tissue, and skeletal muscle, of Otsuka Long-Evans Tokushima Fatty (OLETF) rats. At the age of 6 weeks, RNA was isolated from tissues of fasted OLETF and control LongEvans Tokushima Otsuka (LETO) rats. Gene expression was analyzed using the Agilent rat oligo microarray. Gene ontology analysis showed that gene expression of biologically meaningful groups of genes in liver, adipose tissue, and skeletal muscle, which are involved in the pathogenesis of type 2 diabetes, differed between OLETF and LETO rats. Three hundred genes of whole blood cells were differentially expressed. Four out of these 300 genes were related to the insulin-signaling pathway and 57 out of 300 genes were up-or down-regulated in at least one tissues in OLETF rats. These results support our hypothesis that gene expression profiling of whole blood cells might be a useful source of markers to predict the onset of type 2 diabetes.

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Gene expression profiles in peripheral blood mononuclear cells reflect the pathophysiology of type 2 diabetes

Cited by 73 publications

References 18 publications

Common Transcriptional Signature of Tumor-Infiltrating Mononuclear Inflammatory Cells and Peripheral Blood Mononuclear Cells in Hepatocellular Carcinoma Patients

Common Transcriptional Signature of Tumor-Infiltrating Mononuclear Inflammatory Cells and Peripheral Blood Mononuclear Cells in Hepatocellular Carcinoma Patients

Microarray-based identification of novel biomarkers in IL-1-mediated diseases

DNA Microarray Analysis of Whole Blood Cells and Insulin-Sensitive Tissues Reveals the Usefulness of Blood RNA Profiling as a Source of Markers for Predicting Type 2 Diabetes

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