BACKGROUND/AIMS: 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.
BACKGROUND/AIMS: 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: Paul C Schröder; Víctor Segura; José Ignacio Riezu; Bruno Sangro; José M Mato; Jesús Prieto; Enrique Santamaría; Fernando J Corrales Journal: Funct Integr Genomics Date: 2011-05-12 Impact factor: 3.410
Authors: Igor P Pogribny; Athena Starlard-Davenport; Volodymyr P Tryndyak; Tao Han; Sharon A Ross; Ivan Rusyn; Frederick A Beland Journal: Lab Invest Date: 2010-06-14 Impact factor: 5.662
Authors: Eva Rodríguez-Suárez; Antonio M Duce; Juan Caballería; Félix Martínez Arrieta; Estefanía Fernández; Carolina Gómara; Nere Alkorta; Usue Ariz; M Luz Martínez-Chantar; Shelly C Lu; Felix Elortza; José M Mato Journal: Proteomics Clin Appl Date: 2010-02-03 Impact factor: 3.494
Authors: Xabier Buqué; María José Martínez; Ainara Cano; María E Miquilena-Colina; Carmelo García-Monzón; Patricia Aspichueta; Begoña Ochoa Journal: J Lipid Res Date: 2009-09-24 Impact factor: 5.922
Authors: Javier Conde-Vancells; Eva Rodriguez-Suarez; Nieves Embade; David Gil; Rune Matthiesen; Mikel Valle; Felix Elortza; Shelly C Lu; Jose M Mato; Juan M Falcon-Perez Journal: J Proteome Res Date: 2008-12 Impact factor: 4.466
Authors: April D Lake; Petr Novak; Craig D Fisher; Jonathan P Jackson; Rhiannon N Hardwick; D Dean Billheimer; Walter T Klimecki; Nathan J Cherrington Journal: Drug Metab Dispos Date: 2011-07-07 Impact factor: 3.922