Type 1 diabetes human enteroid studies reveal major changes in the intestinal epithelial compartment.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
24 May 2024
24 May 2024
Historique:
received:
02
02
2024
accepted:
15
05
2024
medline:
25
5
2024
pubmed:
25
5
2024
entrez:
24
5
2024
Statut:
epublish
Résumé
Lack of understanding of the pathophysiology of gastrointestinal (GI) complications in type 1 diabetes (T1D), including altered intestinal transcriptomes and protein expression represents a major gap in the management of these patients. Human enteroids have emerged as a physiologically relevant model of the intestinal epithelium but establishing enteroids from individuals with long-standing T1D has proven difficult. We successfully established duodenal enteroids using endoscopic biopsies from pediatric T1D patients and compared them with aged-matched enteroids from healthy subjects (HS) using bulk RNA sequencing (RNA-seq), and functional analyses of ion transport processes. RNA-seq analysis showed significant differences in genes and pathways associated with cell differentiation and proliferation, cell fate commitment, and brush border membrane. Further validation of these results showed higher expression of enteroendocrine cells, and the proliferating cell marker Ki-67, significantly lower expression of NHE3, lower epithelial barrier integrity, and higher fluid secretion in response to cAMP and elevated calcium in T1D enteroids. Enteroids established from pediatric T1D duodenum identify characteristics of an abnormal intestinal epithelium and are distinct from HS. Our data supports the use of pediatric enteroids as an ex-vivo model to advance studies of GI complications and drug discovery in T1D patients.
Identifiants
pubmed: 38789719
doi: 10.1038/s41598-024-62282-x
pii: 10.1038/s41598-024-62282-x
doi:
Substances chimiques
Sodium-Hydrogen Exchanger 3
0
SLC9A3 protein, human
0
Ki-67 Antigen
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
11911Subventions
Organisme : NIH HHS
ID : R01-DK-116352
Pays : United States
Organisme : NIH HHS
ID : R01-DK-116352
Pays : United States
Organisme : NIH HHS
ID : R01-DK-116352
Pays : United States
Organisme : National Institute of Health
ID : P30-DK-89502
Organisme : National Institute of Health
ID : P30-DK-89502
Organisme : Cystic fibrosis foundation grant
ID : SINGHG02020
Organisme : Cystic fibrosis foundation grant
ID : SINGHG02020
Informations de copyright
© 2024. The Author(s).
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