{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T23:20:20Z","timestamp":1789773620497,"version":"4.0.1"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T00:00:00Z","timestamp":1752796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"European Union\u2014Next Generation EU\u2014NRRP M6C2 \u2013 Investment 2.1 Enhancement and strengthening of biomedical research in the NHS","award":["#PNRR-MAD-2022-12375729 (CUP master C43C22001270007)"],"award-info":[{"award-number":["#PNRR-MAD-2022-12375729 (CUP master C43C22001270007)"]}]},{"name":"European Union\u2014Next Generation EU\u2014NRRP M6C2 \u2013 Investment 2.1 Enhancement and strengthening of biomedical research in the NHS","award":["#PNRR-MCNT2-2023-12377779 (CUP master C43C24000410007)"],"award-info":[{"award-number":["#PNRR-MCNT2-2023-12377779 (CUP master C43C24000410007)"]}]},{"name":"IoIBD Operating Grant 2024 to F.U."},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["#RF-2021-12372637 to S.D."],"award-info":[{"award-number":["#RF-2021-12372637 to S.D."]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Crohn\u2019s disease (CD) is a chronic inflammatory disease of the bowel, often complicated by fibrotic strictures, for which medical treatment is lacking, and surgery is commonly required. The mechanisms underlying the progression from chronic inflammation to fibrosis are not yet defined. We aim to unravel CD pathogenesis using a cutting-edge computational pipeline combining several available tools.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Spatial transcriptomics was performed on 13 surgical specimens, including inflamed and fibrotic CD tissues and healthy controls. The resulting spatial data were integrated with single-cell RNA sequencing to trace the cellular and molecular transitions from healthy intestine to fibrotic tissue. Ligand\u2013receptor interaction and pseudotime analyses were employed to infer dynamic cell\u2013cell communication networks and lineage trajectories. Key computational findings were validated through immunostaining in an independent cohort of CD patients. Finally, the therapeutic relevance of the identified target was evaluated in a TNBS-induced chronic colitis mouse model upon CD38 inhibitor administration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We demonstrated that intestinal cytoarchitecture was rearranged while chronic inflammation progressed. CD-associated fibrosis evolved within the mesenchymal compartment, driven by PECAM2 signaling through the PECAM1\u2013CD38 interaction. In parallel, ApoA signaling, particularly the APOA1\u2013ABCA interaction, emerged as relevant for maintaining epithelial and stromal homeostasis, while its downregulation was associated with fibrosis development. Moreover, inhibition of CD38 signaling effectively reduced colitis symptoms and colon thickening in the experimental TNBS-induced model of chronic inflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our results provide insights into CD38-driven fibrosis and indicate that blockade of PECAM2 signaling could reduce the development of strictures in patients with CD, potentially offering a new treatment target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ecco-jcc\/jjaf130","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T10:11:00Z","timestamp":1752747060000},"source":"Crossref","is-referenced-by-count":8,"title":["Spatiotemporal analysis of Crohn\u2019s disease reveals PECAM2 signaling at the basis of the inflammation-to-fibrosis transition"],"prefix":"10.1093","volume":"19","author":[{"given":"Luca","family":"Massimino","sequence":"first","affiliation":[{"name":"Gastroenterology and Digestive Endoscopy Department, IRCCS Ospedale San Raffaele , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso Lorenzo","family":"Parigi","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Universit\u00e0 Vita-Salute San Raffaele , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Riva","sequence":"additional","affiliation":[{"name":"Gastroenterology and Digestive Endoscopy Department, IRCCS Ospedale San Raffaele , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Nicol\u00f2","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Universit\u00e0 Vita-Salute San Raffaele , 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