1,721,000 research outputs found
Proteomic Analyses Lead to a Better Understanding of Celiac Disease: Focus on Epitope Recognition and Autoantibodies
No full textProteomic technologies are being used with increasing frequency in the scientific community. In this review, we have highlighted their use in celiac disease (CD). The available techniques, which include two-dimensional (2D) gel electrophoresis, mass spectrometry, and antibody and tissue arrays, have been used to identify proteins or changes in protein expression specific to gut tissue from patients with CD. A number of studies have employed proteomic methodologies to determine the diagnostic biomarkers in body fluids or to examine changes in protein expression and posttranslational modifications during signaling. A fast technological development of these methods, along with the combination of classic techniques with proteomics, will lead to new discoveries, which will consent a better understanding of the pathogenesis of CD
GLIADIN AND TISSUE TRANSGLUTAMINASE MEDIATE PPAR DOWNREGULATION IN INTESTINAL CELLS OF PATIENTS WITH CELIAC DISEASE
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PPAR Signaling Pathway and Cancer-Related Proteins Are Involved in Celiac Disease-Associated Tissue Damage
No full textCeliac disease (CD) is an immune-mediated disorder triggered by the ingestion of wheat gliadin and related proteins in genetically predisposed individuals. To find a proteomic CD diagnostic signature and to gain a better understanding of pathogenetic mechanisms associated with CD, we analyzed the intestinal mucosa proteome alterations using two dimensional difference gel electrophoresis (2D-DIGE) coupled with matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF ms) of CD patients with varying degrees of histological abnormalities defined by Marsh criteria and controls. Our results clearly evidenced the presence of two groups of patients: Group A, including controls and Marsh 0-1 CD patients; and Group B. consisting of CD subjects with grade II-III Oberhuber-Marsh classification. Differentially expressed proteins were involved mainly in lipid, protein and sugar metabolism. Interestingly, in Group B, several downregulated proteins (FABP1, FABP2, APOC3, HMGCS2, ACADM and PEPCK) were implicated directly in the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Moreover, Group B patients presented a deregulation of some proteins involved in apoptosis/survival pathways: phosphatidylethanolamine-binding protein 1 (PEBP1), Ras-related nuclear protein (Ran) and peroxiredoxin 4 (PRDX4). PEBP1 downregulation and RAN and PRDX4 upregulation were associated with more severe tissue damage. Likewise, IgMs were found strongly upregulated in Group B. In conclusion, our results indicate that a downregulation of proteins involved in PPAR signaling and the modulation of several cancer-related proteins are associated with the highest CD histological score according to Oberhuber-Marsh classification. (C) 2010 The Feinstein Institute for Medical Research, www.feinsteininstitute.or
Galectin-10, Eosinophils, and Celiac Disease
No full textCeliac disease (CD) is a chronic intestinal disease caused by intolerance to dietary wheat gluten in genetically susceptible individuals. There are a number of important open questions that impede the full explanation of the pathogenesis of this disease. We analyzed protein expression pattern in gut biopsies of CD subjects. Patients were selected and grouped according to histological inflammatory degree. Groups consisted of nine individuals with CD: three patients had a Marsh 0, three a Marsh I-II, and three a Marsh III. All CD patients showed a human leukocyte antigen DQ2/8 variant. Controls were three individuals with an excluded CD diagnosis. For the first time, galectin-10 expression was found related to the histological grade (P = 0.0092) and with the number of eosinophils in the lesion (P = 0.0040). Results suggest galectin-10 is a novel marker for evaluating CD tissue damage and eosinophils as a possible target for therapeutic approaches. Moreover, our data provide insights into alterations associated with CD tissue damage and pathogenesis
Relationship between galectin-10 expression and severity of celiac disease abolished in the presence of gamma/delta plus T cell clonal expansion
No full textDo gliadin and tissue transglutaminase mediate PPAR downregulation in intestinal cells of patients with coeliac disease?
No full textRelationship between Galectin-10 expression and severity of celiac disease abolished in the presence of gamma delta-positive T cell clonal expansion
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