title: Mitochondrial-related gene expression profiles suggest an important role of PGC-1alpha in the compensatory mechanism of endemic dilated cardiomyopathy.
abstract: Keshan disease (KD) is an endemic dilated cardiomyopathy with unclear etiology. In this study, we compared mitochondrial-related gene expression profiles of peripheral blood mononuclear cells (PBMCs) derived from 16 KD patients and 16 normal controls in KD areas. Total RNA was isolated, amplified, labeled and hybridized to Agilent human 4 × 44k whole genome microarrays. Mitochondrial-related genes were screened out by the Third-Generation Human Mitochondria-Focused cDNA Microarray (hMitChip3). Quantitative real-time PCR, immunohistochemical and biochemical parameters related mitochondrial metabolism were conducted to validate our microarray results. In KD samples, 34 up-regulated genes (ratios ≥ 2.0) were detected by significance analysis of microarrays and ingenuity systems pathway analysis (IPA). The highest ranked molecular and cellular functions of the differentially regulated genes were closely related to amino acid metabolism, free radical scavenging, carbohydrate metabolism, and energy production. Using IPA, 40 significant pathways and four significant networks, involved mainly in apoptosis, mitochondrion dysfunction, and nuclear receptor signaling were identified. Based on our results, we suggest that PGC-1alpha regulated energy metabolism and anti-apoptosis might play an important role in the compensatory mechanism of KD. Our results may lead to the identification of potential diagnostic biomarkers for KD in PBMCs, and may help to understand the pathogenesis of KD.
authors: Key Laboratory of Environment and Gene Related Diseases, Xi'an Jiaotong University, Ministry Education, No. 76 Yanta West Road, Xi'an, Shaanxi 710061, PR China; Key Laboratory of Trace Elements and Endemic Diseases, Xi'an Jiaotong University, Ministry of Health, No. 76 Yanta West Road, Xi'an, Shaanxi 710061, PR China.
authors: Shu-Lan
authors: SL
authors: He
authors: Wu-Hong
authors: WH
authors: Tan
authors: Zeng-Tie
authors: ZT
authors: Zhang
authors: Feng
authors: F
authors: Zhang
authors: Cheng-Juan
authors: CJ
authors: Qu
authors: Yan-Xia
authors: YX
authors: Lei
authors: Yan-He
authors: YH
authors: Zhu
authors: Han-Jie
authors: HJ
authors: Yu
authors: You-Zhang
authors: YZ
authors: Xiang
authors: Xiong
authors: X
authors: Guo
mesh_terms: D000328:Adult; D009202:Cardiomyopathies / Q000235:genetics*; D016022:Case-Control Studies; D004769:Enterovirus Infections / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D050259:Genes, Mitochondrial; D006801:Humans; D008297:Male; D008875:Middle Aged; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors
keywords: Immunohistochemical (IHC); Ingenuity systems pathway analysis (IPA); Keshan disease (KD); Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1alpha); Significance analysis of microarrays (SAM)