biostudies-literatureLaudisi FMinistero dell'Università e della Ricerca18https://www.ebi.ac.uk/biostudies/studies/S-EPMC12914907biostudies-literatureUnknown33(1)<h4>Background and aims</h4>Defects of the gut epithelial barrier and counter-regulatory mechanisms are a prerequisite for the onset of intestinal inflammation in patients with inflammatory bowel diseases (IBD). Elevated levels of Smad7, an inhibitor of TGF-β1, in both epithelial and immune cells have been associated with the pathological processes observed in IBD. We aim to determine the relevance of Smad7 expression in the epithelial compartment.<h4>Methods</h4>We generated mice overexpressing Smad7 in the gut epithelium (Smad7TgCre⁺) and monitored pathology development. Inflammatory cell infiltration was assessed using multiplex immunofluorescence and flow cytometry. To investigate the molecular mechanisms underlying ileal damage, we performed spatial transcriptomics on frozeJournal of biomedical scienceIntestinal epithelial Smad7 drives purine metabolic dysregulation and ileal inflammation.PMC12914907PNRR M4C2I1.3 PE6 project PE00000019 Heal ItaliaPRIN 2022JEBP88,Villablanca EJStolfi CZorzi FHe NSica GSMelaiu OMonasterio GSommella EMFantini MCPacifico TMonteleone ISerra MATomassini LOrtenzi AD'Oria VMonteleone GLaudisi FDe Stefanis CfalseIntestinal epithelial Smad7 drives purine metabolic dysregulation and ileal inflammation.<h4>Background and aims</h4>Defects of the gut epithelial barrier and counter-regulatory mechanisms are a prerequisite for the onset of intestinal inflammation in patients with inflammatory bowel diseases (IBD). Elevated levels of Smad7, an inhibitor of TGF-β1, in both epithelial and immune cells have been associated with the pathological processes observed in IBD. We aim to determine the relevance of Smad7 expression in the epithelial compartment.<h4>Methods</h4>We generated mice overexpressing Smad7 in the gut epithelium (Smad7TgCre⁺) and monitored pathology development. Inflammatory cell infiltration was assessed using multiplex immunofluorescence and flow cytometry. To investigate the molecular mechanisms underlying ileal damage, we performed spatial transcriptomics on froze2026-01-01T00:00:00Z2026 Feb2026-07-16T06:30:55.512Z2026-07-09T10:39:09.506ZS-EPMC129149074170357410.1186/s12929-026-01224-3