Browsing by Subject "Gene expression profile"

Now showing 1 - 3 of 3
  • Thumbnail Image
    Publication
    Open Access
    A role for mammalian target of rapamycin -mTOR- pathway in non alcoholic steatohepatitis related-cirrhosis
    (Murcia : F. Hernández, 2010) Kubrusly, Márcia Saldanha; Corrêa-Giannella, Maria Lúcia; Bellodi-Privato, Marta; de Sá, Sandra Valéria; Cauduro Soares, Iberê; Wakamatsu, Alda; Avancini Ferreira Alves, Venâncio; Giannella-Neto, Daniel; Bacchella, Telesforo; Cerqueira Cesar Machado, Marcel; Carneiro D’Albuquerque, Luiz Augusto; Pinto Marques Souza de Oliveira, Claudia
    Summary. Non-alcoholic fatty liver disease (NAFLD) encompasses the whole spectrum of steatosis, nonalcoholic steatohepatitis (NASH), and NASH-related cirrhosis (NASH/Cir). Although molecular advances have been made in this field, the pathogenesis of NAFLD is not completely understood. The gene expression profiling associated to NASH/Cir was assessed, in an attempt to better characterize the pathways involved in its etiopathogenesis. Methods: In the first step, we used cDNA microarray to evaluate the gene expression profiles in normal liver (n=3) and NASH/Cir samples (n=3) by GeneSifter™ analysis to identify differentially expressed genes and biological pathways. Second, tissue microarray was used to determine immunohistochemical expression of phosphorylated mTOR and 4E-BP1 in 11 normal liver samples, 10 NASH/Cir samples and in 37 samples of cirrhosis of other etiologies to further explore the involvement of the mTOR pathway evidenced by the gene expression analysis. Results: 138 and 106 genes were, respectively, up and down regulated in NASH/Cir in comparison to normal liver. Among the 9 pathways identified as significantly modulated in NASH/Cir, the participation of the mTOR pathway was confirmed, since expression of cytoplasmic and membrane phosphomTOR were higher in NASH/Cir in comparison to cirrhosis of other etiologies and to normal liver. Conclusions: Recent findings have suggested a role for the cellular “nutrient sensor” mTOR in NAFLD and the present study corroborates the participation of this pathway in NASH/Cir. Phospho-mTOR evaluation might be of clinical utility as a potential marker for identification of NASH/Cir in cases mistakenly considered as cryptogenic cirrhosis owing to paucity of clinical data.
  • Thumbnail Image
    Publication
    Open Access
    Dissecting the transcriptional program of phosphomannomutase 2-deficient cells: Lymphoblastoide B cell lines as a valuable model for congenital disorders of glycosylation studies
    (2021) Parrado González, Antonio; Serrano Gimaré, M.; De La Morena Barrio, M. E.; Ibañez Micó, S.; Ruiz Lafuente, N.; Schwartz-albiez, R.; Esteve Solé, A.; Alsina Manrique De Lara, L.; Corral de la Calle, Javier; Hernández Caselles, Trinidad; Rubio Pedraza, Gonzalo; Bioquímica y Biología Molecular B e Inmunología
    Congenital disorders of glycosylation (CDG) include 150 disorders constituting in genetically and clinically heterogeneous diseases, showing significant glycoprotein hypoglycosylation that leads to pathological consequences on multiple organs and systems whose underlying mechanisms are not yet understood. A few cellular and animal models have been used to study specific CDG characteristics, although they have given limited information due to the few CDG mutations tested and the still missing comprehensive molecular and cellular basic research. Here, we provide specific gene expression profiles, based on ribonucleic acid (RNA) microarray analysis, together with some biochemical and cellular characteristics of a total of nine control Epstein– Barr virus-transformed lymphoblastoid B cell lines (B-LCL) and 13 CDG B-LCL from patients carrying severe mutations in the phosphomannomutase 2 (PMM2) gene, strong serum protein hypoglycosylation and neurological symptoms. Significantly dysregulated genes in PMM2-CDG cells included those regulating stress responses, transcription factors, glycosylation, motility, cell junction and, importantly, those related to development and neuronal differentiation and synapse, such as carbonic anhydrase 2 (CA2) and ADAM23. PMM2-CDG-associated biological consequences involved the unfolded protein response, RNA metabolism and the endoplasmic reticulum, Golgi apparatus and mitochondria components. Changes in the transcriptional and CA2 protein levels are consistent with the CDG physiopathology. These results demonstrate the global transcriptional impact in phosphomannomutase 2-deficient cells, reveal CA2 as a potential cellular biomarker and confirm B-LCL as an advantageous model for CDG studies.
  • Thumbnail Image
    Publication
    Open Access
    Dissecting the transcriptional program of phosphomannomutase 2-deficient cells: Lymphoblastoide B cell lines as a valuable model for congenital disorders of glycosylation studies
    (Oxford University Press, 2022) Parrado, Antonio; Serrano, Mercedes; De la Morena-Barrio, María Eugenia; Ibáñez-Micó, Salvador; Ruiz-Lafuente, Natalia; Schwartz-Albiez, Reinhard; Esteve-Solé, Ana; Alsina, Laia; Corral, Javier; Hernández Caselles, Trinidad; Rubio Pedraza, Gonzalo; Bioquímica y Biología Molecular B e Inmunología
    Congenital disorders of glycosylation (CDG) include 150 disorders constituting in genetically and clinically heterogeneous diseases, showing significant glycoprotein hypoglycosylation that leads to pathological consequences on multiple organs and systems whose underlying mechanisms are not yet understood. A few cellular and animal models have been used to study specific CDG characteristics, although they have given limited information due to the few CDG mutations tested and the still missing comprehensive molecular and cellular basic research. Here, we provide specific gene expression profiles, based on ribonucleic acid (RNA) microarray analysis, together with some biochemical and cellular characteristics of a total of nine control Epstein– Barr virus-transformed lymphoblastoid B cell lines (B-LCL) and 13 CDG B-LCL from patients carrying severe mutations in the phosphomannomutase 2 (PMM2) gene, strong serum protein hypoglycosylation and neurological symptoms. Significantly dysregulated genes in PMM2-CDG cells included those regulating stress responses, transcription factors, glycosylation, motility, cell junction and, importantly, those related to development and neuronal differentiation and synapse, such as carbonic anhydrase 2 (CA2) and ADAM23. PMM2-CDG-associated biological consequences involved the unfolded protein response, RNA metabolism and the endoplasmic reticulum, Golgi apparatus and mitochondria components. Changes in the transcriptional and CA2 protein levels are consistent with the CDG physiopathology. These results demonstrate the global transcriptional impact in phosphomannomutase 2-deficient cells, reveal CA2 as a potential cellular biomarker and confirm B-LCL as an advantageous model for CDG studies.