title: Hemodialysis modulates gene expression profile in skeletal muscle.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Nephrology and Department of Medicine, University of New Mexico, Albuquerque, NM 87131, USA.
authors.forename: Vallabh O
authors.initials: VO
authors.lastname: Shah
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Dominic
authors.forename: Pope
authors.initials: P
authors.lastname: Moseley
authors.forename: Gavin
authors.initials: G
authors.lastname: Pickett
authors.forename: Margret
authors.initials: M
authors.lastname: Fleet
authors.forename: Scott
authors.initials: S
authors.lastname: Ness
authors.forename: Dominic S C
authors.initials: DS
authors.lastname: Raj
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000235:genetics / Q000378:metabolism; D000328:Adult; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D015536:Down-Regulation; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D006435:Renal Dialysis; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D014511:Uremia / Q000235:genetics / Q000378:metabolism; D000097642:GADD45 Proteins
chemical_list: D015105:3',5'-Cyclic-AMP Phosphodiesterases; D051743:CCAAT-Enhancer-Binding Protein-delta; D018797:Cell Cycle Proteins; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D017874:Immediate-Early Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; C497252:CEBPD protein, human; C439070:GADD45A protein, human; D000097642:GADD45 Proteins; C098669:TOB1 protein, human; C070114:BTG2 protein, human; C517360:PDE4B protein, human