Comparative expression profiling in the intestine of patients with Giardia-induced postinfectious functional gastrointestinal disorders.

Autor: Martínez C; Department of Human Molecular Genetics, Institute of Human Genetics, Heidelberg University, Heidelberg, Germany.; Lleida Institute for Biomedical Research Dr. Pifarré Foundation (IRBLleida), Lleida, Spain.; Genes in Irritable Bowel Syndrome (GENIEUR) Research Network Europe, Heidelberg, Germany., Lasitschka F; Institute of Pathology, Heidelberg University, Heidelberg, Germany., Thöni C; Institute of Pathology, Heidelberg University, Heidelberg, Germany., Wohlfarth C; Department of Human Molecular Genetics, Institute of Human Genetics, Heidelberg University, Heidelberg, Germany., Braun A; Department of Human Molecular Genetics, Institute of Human Genetics, Heidelberg University, Heidelberg, Germany., Granzow M; Institute of Human Genetics, Heidelberg University, Heidelberg, Germany., Röth R; Department of Human Molecular Genetics, Institute of Human Genetics, Heidelberg University, Heidelberg, Germany.; nCounter Core Facility Heidelberg, Institute of Human Genetics, Heidelberg, Germany., Dizdar V; Department of Clinical Science, University of Bergen, Bergen, Norway., Rappold GA; Department of Human Molecular Genetics, Institute of Human Genetics, Heidelberg University, Heidelberg, Germany.; nCounter Core Facility Heidelberg, Institute of Human Genetics, Heidelberg, Germany., Hausken T; Genes in Irritable Bowel Syndrome (GENIEUR) Research Network Europe, Heidelberg, Germany.; Department of Medicine, Haukeland University Hospital, Bergen, Norway., Langeland N; Genes in Irritable Bowel Syndrome (GENIEUR) Research Network Europe, Heidelberg, Germany.; Department of Clinical Science, University of Bergen, Bergen, Norway., Hanevik K; Genes in Irritable Bowel Syndrome (GENIEUR) Research Network Europe, Heidelberg, Germany.; Department of Clinical Science, University of Bergen, Bergen, Norway.; Department of Medicine, National Advisory Center for Tropical Infectious Diseases, Haukeland University Hospital, Bergen, Norway., Niesler B; Department of Human Molecular Genetics, Institute of Human Genetics, Heidelberg University, Heidelberg, Germany.; Genes in Irritable Bowel Syndrome (GENIEUR) Research Network Europe, Heidelberg, Germany.; nCounter Core Facility Heidelberg, Institute of Human Genetics, Heidelberg, Germany.
Jazyk: angličtina
Zdroj: Neurogastroenterology and motility [Neurogastroenterol Motil] 2020 Sep; Vol. 32 (9), pp. e13868. Date of Electronic Publication: 2020 May 11.
DOI: 10.1111/nmo.13868
Abstrakt: Background: A Giardia outbreak in Bergen, Norway, caused postinfectious functional gastrointestinal disorders (PI-FGIDs). Despite the devastating effects of this outbreak, it presented a unique chance to investigate the implication on the dysregulation of genetic pathways in PI-FGID.
Methods: We performed the first comparative expression profiling of miRNAs and their potential target genes in microdissected rectal biopsies from 20 Giardia-induced PI-FGID patients vs 18 healthy controls by nCounter analysis. Subsequently, candidates were validated on protein level by immunostaining.
Key Results: miRNA profiling on rectal biopsy samples from 5 diarrhea-predominant PI-IBS cases compared to 10 healthy controls revealed differential expression in the epithelial layer. The top five regulated miRNAs were implicated in GI disease, inflammatory response, and immunological disease. Subsequently, these miRNAs and 100 potential mRNA targets were examined in 20 PI-FGID cases and 18 healthy controls in both the mucosal epithelium and the lamina propria. Although deregulation of the selected miRNAs could not be verified in the larger sample set, mRNAs involved in barrier function were downregulated in the epithelium. Pro-inflammatory genes and genes implicated in epigenetic modifications were upregulated in the lamina propria. Immunostaining for selected candidates on 17 PI-FGID cases and 16 healthy controls revealed increased tryptase levels as well as a decreased and aberrant subcellular expression of occludin.
Conclusions and Inferences: Genes relevant to immune and barrier function as well as stress response and epigenetic modulation are differentially expressed in PI-FGIDs and may contribute to disease manifestation.
(© 2020 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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