title: Identification of a gene-pathway associated with non-alcoholic steatohepatitis.
abstract: OBJECTIVE
  We have integrated gene expression profiling of liver biopsies of NASH patients with liver samples of a mouse model of steatohepatitis (MAT1A-KO) to identify a gene-pathway associated with NASH.
  
  
  METHODS
  Affymetrix U133 Plus 2.0 microarrays were used to evaluate nine patients with NASH, six patients with steatosis, and six control subjects; Affymetrix MOE430A microarrays were used to evaluate wild-type and MAT1A-KO mice at 15 days, 1, 3, 5 and 8 months after birth. Transcriptional profiles of patients with NASH and MAT1A-KO mice were compared with those of their proficient controls.
  
  
  RESULTS
  We identified a gene-pathway associated with NASH, that accurately distinguishes between patients with early-stage NASH and controls. Patients with steatosis have a gene expression pattern intermediate between that of NASH and controls. Promoter analysis revealed that 34 of the genes associated with NASH contained an Sp1 element. We found that Sp1 binding to these genes is increased in MAT1A-KO mice. Sp1 is also hyperphosphorylated in MAT1A-KO as well as in patients with NASH and steatosis.
  
  
  CONCLUSIONS
  A gene-pathway associated with NASH has been identified. We speculate that hyperphosphorylation of Sp1 may be involved in the genesis of steatosis and that other factors, such as oxidative stress, may trigger its progression to NASH.
authors.affiliation: TECNUN, Universidad de Navarra, San Sebastián, Gipuzkoa, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Rubio
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Guruceaga
authors.forename: Mercedes
authors.initials: M
authors.lastname: Vázquez-Chantada
authors.forename: Juan
authors.initials: J
authors.lastname: Sandoval
authors.forename: L Alfonso
authors.initials: LA
authors.lastname: Martínez-Cruz
authors.forename: Victor
authors.initials: V
authors.lastname: Segura
authors.forename: José L
authors.initials: JL
authors.lastname: Sevilla
authors.forename: Adam
authors.initials: A
authors.lastname: Podhorski
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Corrales
authors.forename: Luis
authors.initials: L
authors.lastname: Torres
authors.forename: Manuel
authors.initials: M
authors.lastname: Rodríguez
authors.forename: Fabienne
authors.initials: F
authors.lastname: Aillet
authors.forename: Usue
authors.initials: U
authors.lastname: Ariz
authors.forename: Felix Martínez
authors.initials: FM
authors.lastname: Arrieta
authors.forename: Juan
authors.initials: J
authors.lastname: Caballería
authors.forename: Antonio
authors.initials: A
authors.lastname: Martín-Duce
authors.forename: Shelly C
authors.initials: SC
authors.lastname: Lu
authors.forename: M Luz
authors.initials: ML
authors.lastname: Martínez-Chantar
authors.forename: José M
authors.initials: JM
authors.lastname: Mato
mesh_terms: D000328:Adult; D000818:Animals; D005234:Fatty Liver / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008716:Methionine Adenosyltransferase / Q000172:deficiency; D051379:Mice; D018345:Mice, Knockout; D046228:Microarray Analysis; D008875:Middle Aged; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D016329:Sp1 Transcription Factor / Q000378:metabolism
chemical_list: D016329:Sp1 Transcription Factor; C490703:Mat1a protein, mouse; D008716:Methionine Adenosyltransferase