Gene expression profiles displayed by peripheral blood mononuclear cells from patients with type 2 diabetes mellitus focusing on biological processes implicated on the pathogenesis of the disease

Author(s):Show less -

Manoel-Caetano, Fernanda S. ^{[1, 2]} ; Xavier, Danilo J. ^[2] ; Evangelista, Adriane F. ^[2] ; Takahashi, Paula ^[2] ; Collares, Cristhianna V. ^[2] ; Puthier, Denis ^[3] ; Foss-Freitas, Maria C. ^[4] ; Foss, Milton C. ^[4] ; Donadi, Eduardo A. ^[4] ; Passos, Geraldo A. ^{[2, 5]} ; Sakamoto-Hojo, Elza T. ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Dept Biol, Fac Philosophy Sci & Letters Ribeirao Preto, BR-14040901 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Dept Genet, Fac Med Ribeirao Preto, BR-14040901 Ribeirao Preto, SP - Brazil

^[3] Aix Marseille Univ, INSERM, U928, TAGC, IFR137, Marseille - France

^[4] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Clin Med, BR-14040901 Ribeirao Preto, SP - Brazil

^[5] Univ Sao Paulo, Sch Dent Ribeirao Preto, Dept Morphol Stomatol & Physiol, BR-14040901 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Gene; v. 511, n. 2, p. 151-160, DEC 15 2012.
• Web of Science Citations: 26

Abstract

Patients with type 2 diabetes mellitus (T2DM) exhibit insulin resistance associated with obesity and inflammatory response, besides an increased level of oxidative DNA damage as a consequence of the hyperglycemic condition and the generation of reactive oxygen species (ROS). In order to provide information on the mechanisms involved in the pathophysiology of T2DM, we analyzed the transcriptional expression patterns exhibited by peripheral blood mononuclear cells (PBMCs) from patients with T2DM compared to non-diabetic subjects, by investigating several biological processes: inflammatory and immune responses, responses to oxidative stress and hypoxia, fatty acid processing, and DNA repair. PBMCs were obtained from 20 T2DM patients and eight non-diabetic subjects. Total RNA was hybridized to Agilent whole human genome 4x44K one-color oligo-microarray. Microarray data were analyzed using the GeneSpring GX 11.0 software (Agilent). We used BRB-ArrayTools software (gene set analysis - GSA) to investigate significant gene sets and the Genomica tool to study a possible influence of clinical features on gene expression profiles. We showed that PBMCs from T2DM patients presented significant changes in gene expression, exhibiting 1320 differentially expressed genes compared to the control group. A great number of genes were involved in biological processes implicated in the pathogenesis of T2DM. Among the genes with high fold-change values, the up-regulated ones were associated with fatty acid metabolism and protection against lipid-induced oxidative stress, while the down-regulated ones were implicated in the suppression of pro-inflammatory cytokines production and DNA repair. Moreover, we identified two significant signaling pathways: adipocytokine, related to insulin resistance; and ceramide, related to oxidative stress and induction of apoptosis. In addition, expression profiles were not influenced by patient features, such as age, gender, obesity, pre/post-menopause age, neuropathy, glycemia, and HbA(1c) percentage. Hence, by studying expression profiles of PBMCs, we provided quantitative and qualitative differences and similarities between T2DM patients and non-diabetic individuals, contributing with new perspectives for a better understanding of the disease. (C) 2012 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 08/56594-8 - Control of the transcriptome in diabetes mellitus
• Grantee: Geraldo Aleixo da Silva Passos Júnior
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 10/12069-7 - Gene expression profiles and possible interactions between microRNAs and mRNAs in type 1 Diabetes Mellitus, focusing on response to oxidative stress and DNA repair
• Grantee: Paula Takahashi
• Support type: Scholarships in Brazil - Doctorate