Sandra Pérez-Torras1, Ingrid Iglesias2, Marta Llopis3, Juan J Lozano4, María Antolín3, Francisco Guarner3, Marçal Pastor-Anglada2. 1. Molecular Pharmacology and Experimental Therapeutics, Department of Biochemistry and Molecular Biology, Institute of Biomedicine, University of Barcelona, Barcelona, Spain Oncology Program, CIBERehd, National Biomedical Research Institute on Liver and Gastrointestinal Diseases, Instituto de Salud Carlos III, Barcelona, Spain s.perez-torras@ub.edu. 2. Molecular Pharmacology and Experimental Therapeutics, Department of Biochemistry and Molecular Biology, Institute of Biomedicine, University of Barcelona, Barcelona, Spain Oncology Program, CIBERehd, National Biomedical Research Institute on Liver and Gastrointestinal Diseases, Instituto de Salud Carlos III, Barcelona, Spain. 3. Digestive System Research Unit, University Hospital Vall d'Hebron, CIBEREHD, Passeig Vall d'Hebron 119-129, Barcelona 08035, Spain. 4. Bioinformatics Platform, CIBERehd, Barcelona, Spain.
Abstract
BACKGROUND AND AIMS: Several transport alterations have been described in intestinal inflammatory diseases. This is relevant because the primary function of the intestine is nutrient and mineral absorption. However, analysis of the transportome as a whole and the effect of commensal bacteria on it have not been addressed so far. METHODS: Five healthy and 6 Crohn's disease (CD) samples were hybridized to human HT-12 V4 Illumina GeneChip. Results were validated by reverse transcription-polymerase chain reaction (RT-PCR) analysis and with additional array data. Organ culture assays were performed from mucosa ileal wall specimens collected at surgery. Samples were incubated with or without commensal bacteria for 4 hours. Finally, RNA was isolated for microarray processing. RESULTS: The analysis of CD versus healthy ileal mucosa demonstrated upregulation of previously described genes involved in immunity and the inflammatory response in this disease. Interestingly, whole transcriptional analysis revealed profound alterations in the transportome profile. Sixty-two solute carrier (SLC) transporters displayed different expression patterns, most of them being downregulated. Changes were confirmed by RT-PCR in a randomly chosen subset of SLCs. A large number of amino acid transporters and most members of the enteric purinome were found to be altered. Most of these proteins were found at the apical membrane of the enterocyte, which could impair both amino acid absorption and purinergic signalling. Treatment of ileum specimen explants with commensal bacteria restored almost all CD transportome alterations. CONCLUSIONS: These results describe the altered transportome profile in CD and open the possibility of restoring transportome complications with commensal bacteria.
BACKGROUND AND AIMS: Several transport alterations have been described in intestinal inflammatory diseases. This is relevant because the primary function of the intestine is nutrient and mineral absorption. However, analysis of the transportome as a whole and the effect of commensal bacteria on it have not been addressed so far. METHODS: Five healthy and 6 Crohn's disease (CD) samples were hybridized to human HT-12 V4 Illumina GeneChip. Results were validated by reverse transcription-polymerase chain reaction (RT-PCR) analysis and with additional array data. Organ culture assays were performed from mucosa ileal wall specimens collected at surgery. Samples were incubated with or without commensal bacteria for 4 hours. Finally, RNA was isolated for microarray processing. RESULTS: The analysis of CD versus healthy ileal mucosa demonstrated upregulation of previously described genes involved in immunity and the inflammatory response in this disease. Interestingly, whole transcriptional analysis revealed profound alterations in the transportome profile. Sixty-two solute carrier (SLC) transporters displayed different expression patterns, most of them being downregulated. Changes were confirmed by RT-PCR in a randomly chosen subset of SLCs. A large number of amino acid transporters and most members of the enteric purinome were found to be altered. Most of these proteins were found at the apical membrane of the enterocyte, which could impair both amino acid absorption and purinergic signalling. Treatment of ileum specimen explants with commensal bacteria restored almost all CD transportome alterations. CONCLUSIONS: These results describe the altered transportome profile in CD and open the possibility of restoring transportome complications with commensal bacteria.
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