Hemodialysis modulates gene expression profile in skeletal muscle.
Am J Kidney Dis
; 48(4): 616-28, 2006 Oct.
Article
em En
| MEDLINE
| ID: mdl-16997058
ABSTRACT
BACKGROUND:
Uremia alters diverse metabolic pathways involving multiple organ systems, including skeletal muscle. Skeletal muscle has an important role in nutrition, metabolism, oxidative stress, and inflammation. We hypothesized that hemodialysis (HD) will change the genomic fingerprinting associated with uremia and facilitate expression of a distinct set of genes.METHODS:
Five patients with end-stage renal disease (ESRD) were studied. Skeletal muscle biopsy specimens from the vastus lateralis were obtained before (pre-HD) and during the last 10 minutes of HD (post-HD). Oligonucleotide microarray (version 2, GeneChip arrays; Affymetrix U95A, Santa Clara, CA) was used to analyze global transcriptional modification in skeletal muscle by HD. Pre-HD data were compared with data from 3 subjects without renal failure.RESULTS:
In skeletal muscle of patients with ESRD, 83 genes were upregulated and 8 genes were downregulated pre-HD compared with controls. Pathway analysis linked 55 genes to 5 gene networks involved in the regulation of cell cycle, cell proliferation, cellular organization, apoptosis, and inflammation. During HD, expression of 22 genes increased and 1 (TOB1) decreased. Pathway analysis mapped 20 genes to 2 genetic networks involved in (1) inflammation, cell proliferation, and cell signaling; and (2) apoptosis, cell function, protein synthesis, and tissue morphology. Reverse-transcription polymerase chain reaction confirmed increased expression of GADD45A, BTG2, PDE4B, and CEBPD and downregulation of TOB1 in skeletal muscle intradialysis.CONCLUSION:
In response to the uremic milieu, skeletal muscle goes through very active transcriptional and translational changes. HD activates a diverse, yet biologically linked, network of genes related to inflammation and apoptosis in skeletal muscle.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Diálise Renal
/
Músculo Esquelético
/
Perfilação da Expressão Gênica
/
Falência Renal Crônica
Idioma:
En
Revista:
Am J Kidney Dis
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos