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Intestinal epithelial Smad7 drives purine metabolic dysregulation and ileal inflammation - PubMed

2 days ago
  • #purine metabolism
  • #IBD
  • #Smad7
  • Elevated Smad7 levels in intestinal epithelial cells (IECs) are linked to inflammatory bowel diseases (IBD).
  • Smad7TgCre+ mice developed spontaneous terminal ileitis, showing villus shortening, mucus depletion, and increased permeability.
  • Altered purine metabolism, particularly reduced CD73 enzyme activity, was observed in Smad7TgCre+ mice, leading to lower adenosine production.
  • Oral adenosine administration restored mucus production and alleviated ileal pathology in Smad7TgCre+ mice.
  • In Crohn's disease (CD) patients, elevated Smad7 correlated with decreased CD73 expression in the inflamed ileum.
  • The study suggests Smad7 overexpression in IECs promotes ileal mucosal damage via impaired purine metabolism.