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There is no pharmacological treatment against this complication, with surgery being the only option. Due to the unknown role of P2X7 in intestinal fibrosis, we aim to analyze the relevance of this receptor in CD complications. Surgical resections from CD and non-Inflammatory Bowel Disease (IBD) patients were obtained. Intestinal fibrosis was induced with two different murine models: heterotopic transplant model and chronic-DSS colitis in wild-type and P2X7-\/- mice. Human small intestine fibroblasts (HSIFs) were transfected with an siRNA against P2X7 and treated with TGF-\u03b2. A gene and protein expression of P2X7 receptor was significantly increased in CD compared to non-IBD patients. The lack of P2X7 in mice provoked an enhanced collagen deposition and increased expression of several profibrotic markers in both murine models of intestinal fibrosis. Furthermore, P2X7-\/- mice exhibited a higher expression of proinflammatory cytokines and a lower expression of M2 macrophage markers. Moreover, the transient silencing of the P2X7 receptor in HSIFs significantly induced the expression of Col1a1 and potentiated the expression of Col4 and Col5a1 after TGF-\u03b2 treatment. P2X7 regulates collagen expression in human intestinal fibroblasts, while the lack of this receptor aggravates intestinal fibrosis.<\/jats:p>","DOI":"10.3390\/ijms241612936","type":"journal-article","created":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T09:13:44Z","timestamp":1692350024000},"page":"12936","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["P2X7 Receptor Regulates Collagen Expression in Human Intestinal Fibroblasts: Relevance in Intestinal Fibrosis"],"prefix":"10.3390","volume":"24","author":[{"given":"Lluis","family":"Lis-L\u00f3pez","sequence":"first","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Bauset","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4278-2835","authenticated-orcid":false,"given":"Marta","family":"Seco-Cervera","sequence":"additional","affiliation":[{"name":"FISABIO (Fundaci\u00f3n para el Fomento de la Investigaci\u00f3n Sanitaria y Biom\u00e9dica), Hospital Dr. Peset, 46017 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dulce","family":"Macias-Ceja","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9775-3169","authenticated-orcid":false,"given":"Francisco","family":"Navarro","sequence":"additional","affiliation":[{"name":"Servicio Cirug\u00eda y Coloproctolog\u00eda, Hospital de Manises, 46940 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2301-9746","authenticated-orcid":false,"given":"\u00c1ngeles","family":"\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, Spain"},{"name":"CIBERehd (Centro de Investigaciones en Red Enfermedad Hep\u00e1tica y Digestiva), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Vicente","family":"Esplugues","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, Spain"},{"name":"CIBERehd (Centro de Investigaciones en Red Enfermedad Hep\u00e1tica y Digestiva), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9675-2423","authenticated-orcid":false,"given":"Sara","family":"Calatayud","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, Spain"},{"name":"CIBERehd (Centro de Investigaciones en Red Enfermedad Hep\u00e1tica y Digestiva), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Dolores","family":"Barrachina","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, Spain"},{"name":"CIBERehd (Centro de Investigaciones en Red Enfermedad Hep\u00e1tica y Digestiva), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolores","family":"Ortiz-Masi\u00e0","sequence":"additional","affiliation":[{"name":"CIBERehd (Centro de Investigaciones en Red Enfermedad Hep\u00e1tica y Digestiva), 28029 Madrid, Spain"},{"name":"Departamento de Medicina, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Cos\u00edn-Roger","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, Spain"},{"name":"CIBERehd (Centro de Investigaciones en Red Enfermedad Hep\u00e1tica y Digestiva), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"379","DOI":"10.5217\/ir.2019.09148","article-title":"Fibrostenotic strictures in Crohn\u2019s disease","volume":"18","author":"Yoo","year":"2020","journal-title":"Intest. 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