期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
卷 1832, 期 12, 页码 2289-2301出版社
ELSEVIER
DOI: 10.1016/j.bbadis.2013.09.006
关键词
Nuclear receptors; Gene expression; Metabolic Syndrome; Inflammation; Epidemiology
资金
- Italian Association for Cancer Research (AIRC, Milan, Italy) [IG 10410]
- Italian Ministry of University and Education (Finanziamenti per la Ricerca di Base IDEAS) [RBID08C9N7]
- Programma Operativo Nazionale [PON01_01958]
- PRIN [20085Y7XT5_004]
- Italian Ministry of Health [GR-2008-1143546, GR-2010-2314703]
- Apulian Region - Italy [CIP PS_101]
- University of Bari, Italy [ORBA 08WEZJ, 07X7Q1, 06BXVC, IDEA GRBA0802SJ]
- CariSPAQ (L'Aquila, Italy)
Background: Nuclear receptors are a class of 48 ligand-activated transcription factors identified as key players of metabolic and developmental processes. Most of these receptors are potential targets for pharmacological strategies in the Metabolic Syndrome. In the present study, we analyzed changes in the mRNA expression of nuclear receptors in the peripheral blood mononuclear cells of patients with Metabolic Syndrome, in order to identify novel biomarkers of disease and candidate targets for putative therapeutical approaches. Methods and results: We enrolled thirty healthy controls (14 M:16 F) and thirty nave patients (16 M: 14 F; >3 criteria for Metabolic Syndrome upon Adult Treatment Panel 111) without organ damage. Using quantitative real-time PCR, we assessed the expression patterns of nuclear receptors in peripheral blood mononuclear cells. 33/48 nuclear receptors were expressed in peripheral blood mononuclear cells. In patients with Metabolic Syndrome, we found a significant down-regulation of the entire PPAR, NR4A and RAR families, together with a repression of RXR alpha, VDR, and Rev-Erb alpha. Furthermore, we performed a novel statistical analysis with classification trees, which allowed us to depict a predictive core of nuclear receptor expression patterns characterizing subjects with Metabolic Syndrome. Random Forest Analysis identified NOR1 and PEAR delta, which were both reduced in peripheral blood mononuclear cells and specifically in CD14(+) cells (mostly monocytes), as classifiers of Metabolic Syndrome, with high specificity and sensitivity. Conclusions: Our results point to the use of PPAR and NR4A mRNA levels in the overall peripheral blood mononuclear cells as biomarkers of Metabolic Syndrome and bona fide putative targets of pharmacological therapy. (C) 2013 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据