{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T22:24:43Z","timestamp":1789424683152,"version":"build-2803163510"},"reference-count":70,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T00:00:00Z","timestamp":1676419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Celiac disease (CD) is a chronic and systemic autoimmune disorder that affects preferentially the small intestine of individuals with a genetic predisposition. CD is promoted by the ingestion of gluten, a storage protein contained in the endosperm of the seeds of wheat, barley, rye, and related cereals. Once in the gastrointestinal (GI) tract, gluten is enzymatically digested with the consequent release of immunomodulatory and cytotoxic peptides, i.e., 33mer and p31-43. In the late 1970s a new group of biologically active peptides, called gluten exorphins (GEs), was discovered and characterized. In particular, these short peptides showed a morphine-like activity and high affinity for the \u03b4-opioid receptor (DOR). The relevance of GEs in the pathogenesis of CD is still unknown. Recently, it has been proposed that GEs could contribute to asymptomatic CD, which is characterized by the absence of symptoms that are typical of this disorder. In the present work, GEs cellular and molecular effects were in vitro investigated in SUP-T1 and Caco-2 cells, also comparing viability effects with human normal primary lymphocytes. As a result, GEs treatments increased tumor cell proliferation by cell cycle and Cyclins activation as well as by induction of mitogenic and pro-survival pathways. Finally, a computational model of GEs interaction with DOR is provided. Altogether, the results might suggest a possible role of GEs in CD pathogenesis and on its associated cancer comorbidities.<\/jats:p>","DOI":"10.3390\/ijms24043912","type":"journal-article","created":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T05:12:26Z","timestamp":1676437946000},"page":"3912","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Gluten Exorphins Promote Cell Proliferation through the Activation of Mitogenic and Pro-Survival Pathways"],"prefix":"10.3390","volume":"24","author":[{"given":"Federico","family":"Manai","sequence":"first","affiliation":[{"name":"Department of Biology and Biotechnology \u201cL.Spallanzani\u201d, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Zanoletti","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology \u201cL.Spallanzani\u201d, University of Pavia, 27100 Pavia, Italy"},{"name":"Laboratory for Mucosal Immunology, TARGID, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9681-7845","authenticated-orcid":false,"given":"Giulia","family":"Morra","sequence":"additional","affiliation":[{"name":"SCITEC, Consiglio Nazionale delle Ricerche, 20131 Milano, Italy"},{"name":"Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samman","family":"Mansoor","sequence":"additional","affiliation":[{"name":"SCITEC, Consiglio Nazionale delle Ricerche, 20131 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Carriero","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology \u201cL.Spallanzani\u201d, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5947-2414","authenticated-orcid":false,"given":"Elena","family":"Bozzola","sequence":"additional","affiliation":[{"name":"Pediatric Unit, I.R.C.C.S. Bambino Ges\u00f9 Children Hospital, 00165 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella","family":"Muscianisi","sequence":"additional","affiliation":[{"name":"Cell Factory and Pediatric Hematology\/Oncology, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7568-1144","authenticated-orcid":false,"given":"Sergio","family":"Comincini","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology \u201cL.Spallanzani\u201d, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1016\/S0140-6736(09)60254-3","article-title":"Coeliac disease","volume":"373","author":"Corazza","year":"2009","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1111\/j.1365-2249.2005.02783.x","article-title":"The immune recognition of gluten in coeliac disease","volume":"140","author":"Ciccocioppo","year":"2005","journal-title":"Clin. 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