Underexpression of mitochondrial-DNA encoded ATP synthesis-related genes and DNA repair genes in systemic lupus erythematosusReportar como inadecuado




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Arthritis Research and Therapy

, 13:R63

First Online: 15 April 2011Received: 06 January 2011Revised: 11 March 2011Accepted: 15 April 2011

Abstract

IntroductionSystemic lupus erythematosus SLE is a prototypical autoimmune disease characterized by various systemic symptoms and multiple organ damage. We clarify biological and functional abnormalities in SLE by comparing the gene expression profiles of SLE patients with those of healthy individuals.

MethodsGene expression profiles from the peripheral blood of 21 SLE patients and 45 healthy individuals were obtained using a DNA microarray. Gene ontology analysis and network pathway analysis were performed on the genes differentially expressed between SLE and healthy individuals.

ResultsA total of 2,329 upregulated genes and 1,884 downregulated genes were differentially expressed. Gene ontology analysis revealed that the upregulated genes were classified as response to biotic stimulus genes, which mainly includes genes related to immune response. Abnormalities in other categories such as cell motility and regulation of apoptosis were also revealed. Downregulated genes were mainly sorted into two gene categories, sensory perception and response to radiation-light. The sensory perception genes included ATPase-ATPase domain-containing genes, myosin-related genes, and two excision repair cross-complementing genes, which are involved in DNA repair. Other genes in this group - including three crystallin genes, genes encoding the receptor protein for melanocyte-stimulating hormone, and six mitochondrial-DNA encoded genes, which are involved in ATP synthesis - were also categorized as response to radiation genes. Using network pathway analysis, IL-6, transforming growth factor beta 1, TNF, and hepatocyte nuclear factor 4α were found to play central roles in the networks of sensory perception-related molecules.

ConclusionsFunctional abnormalities in ATP synthesis and DNA repair are implicated in peripheral blood cells from SLE patients.

AbbreviationsaRNAamino allyl RNA

ATP6ATP synthase 6

CASPcaspase

COXcytochrome c oxidase

CYTBcytochrome b

EASEExpression Analysis Systematic Explorer

ERCCexcision repair cross-complementing

IFNinterferon

ILinterleukin

mtDNAmitochondrial DNA

NDNADH dehydrogenase subunit

NF-κBnuclear factor of kappa light polypeptide

OPA1optic atrophy 1

SLEsystemic lupus erythematosus

SLEDAISLE Disease Activity Index

TNFtumor necrosis factor

XPDxeroderma pigmentosum complementation group D

XPGxeroderma pigmentosum complementation group G.

Electronic supplementary materialThe online version of this article doi:10.1186-ar3317 contains supplementary material, which is available to authorized users.

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Autor: Hooi-Ming Lee - Hidehiko Sugino - Chieko Aoki - Norihiro Nishimoto

Fuente: https://link.springer.com/







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