Comparative expression profiling in the intestine of patients with Giardia-induced postinfectious functional gastrointestinal disorders.
expression analysis
laser-capture microdissection
leaky gut
mast cells
occludin
postinfectious functional GI disorders
tight junctions
tryptase
Journal
Neurogastroenterology and motility
ISSN: 1365-2982
Titre abrégé: Neurogastroenterol Motil
Pays: England
ID NLM: 9432572
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
17
12
2019
revised:
13
03
2020
accepted:
07
04
2020
pubmed:
12
5
2020
medline:
29
7
2021
entrez:
12
5
2020
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Substances chimiques
MicroRNAs
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13868Subventions
Organisme : Instituto de Salud Carlos III
ID : CP18/00116
Pays : International
Organisme : Dr.-Robert-Pfleger-Stiftung
ID : NA
Pays : International
Organisme : Helse Vest Bergen Norway
ID : 911897
Pays : International
Organisme : Heidelberg University Hospital
ID : NA
Pays : International
Organisme : Fritz Thyssen Foundation
ID : Az 20.16.0.063MN
Pays : International
Informations de copyright
© 2020 John Wiley & Sons Ltd.
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