title: Expression of proinflammatory factors in renal cortex induced by methylmalonic acid.
abstract: BACKGROUND
  Methylmalonic aciduria is an inborn error of metabolism that causes renal failure and tubulointerstitial (TI) nephritis as complications. This study aimed to examine the levels of expression of several genes related to inflammation, oxidative stress, and mitochondrial function in the renal cortex of rats receiving methylmalonic acid (MMA).
  
  
  METHODS
  Rats received MMA subcutaneously for a month. Tumor necrosis factor alpha (TNFα), nuclear factor-kappa B, interleukin 1 beta (IL-1β), and cyclooxygenase 2 (COX-2) genes were examined by real-time polymerase chain reaction. We also examined transforming growth factor beta (TGF-β) related to TI fibrosis, c-FOS, belonging to the immediate early gene family of transcription factors, and expression of SIRT1, related to energy production.
  
  
  RESULTS
  There was significantly higher expression of TNFα and a trend toward a higher level of TGF-β transcripts in the methylmalonic model group compared with the controls. However, SIRT1 expression was not different among the groups. Urinary MMA excretion correlated positively with mRNA level of TGF-β. The expression of COX-2 was positively associated with the expression of c-FOS and inversely related to the expression of IL-1β.
  
  
  CONCLUSIONS
  The higher levels of TNFα and TGF-β transcripts suggest inflammation and differentiation processes in the renal cortex in rats because of MMA. After 1 month of MMA injections, expression levels of SIRT1 were not affected, suggesting mitochondrial preservation in early stages of the disease.
authors.affiliation: Division of Metabolism, Cruces University Hospital, Barakaldo, Spain.
authors.forename: Estibaliz
authors.initials: E
authors.lastname: Goyenechea
authors.forename: Fernando
authors.initials: F
authors.lastname: Andrade
authors.forename: Javier
authors.initials: J
authors.lastname: de Las Heras
authors.forename: Sergio
authors.initials: S
authors.lastname: Lage
authors.forename: José Ángel
authors.initials: JÁ
authors.lastname: Prieto
authors.forename: Nerea
authors.initials: N
authors.lastname: Ruiz
authors.forename: Luis
authors.initials: L
authors.lastname: Aldámiz-Echevarría
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008764:Methylmalonic Acid / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D010431:Pentoxifylline / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D056564:Sirtuin 1 / Q000378:metabolism
chemical_list: D016207:Cytokines; D016166:Free Radical Scavengers; D016760:Proto-Oncogene Proteins c-fos; D008764:Methylmalonic Acid; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D010431:Pentoxifylline