P2X7 Receptor Regulates Collagen Expression in Human Intestinal Fibroblasts: Relevance in Intestinal Fibrosis
Intestinal fibrosis is a common complication that affects more than 50% of Crohn´s Disease (CD) patients. 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 th...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/16/12936 |
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| author | Lluis Lis-López Cristina Bauset Marta Seco-Cervera Dulce Macias-Ceja Francisco Navarro Ángeles Álvarez Juan Vicente Esplugues Sara Calatayud Maria Dolores Barrachina Dolores Ortiz-Masià Jesús Cosín-Roger |
| author_facet | Lluis Lis-López Cristina Bauset Marta Seco-Cervera Dulce Macias-Ceja Francisco Navarro Ángeles Álvarez Juan Vicente Esplugues Sara Calatayud Maria Dolores Barrachina Dolores Ortiz-Masià Jesús Cosín-Roger |
| author_sort | Lluis Lis-López |
| collection | DOAJ |
| description | Intestinal fibrosis is a common complication that affects more than 50% of Crohn´s Disease (CD) patients. 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-β. 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-β treatment. P2X7 regulates collagen expression in human intestinal fibroblasts, while the lack of this receptor aggravates intestinal fibrosis. |
| first_indexed | 2024-03-10T23:52:52Z |
| format | Article |
| id | doaj.art-e9054f54e6c24668bbf7926cd849c5ec |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T23:52:52Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e9054f54e6c24668bbf7926cd849c5ec2023-11-19T01:32:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124161293610.3390/ijms241612936P2X7 Receptor Regulates Collagen Expression in Human Intestinal Fibroblasts: Relevance in Intestinal FibrosisLluis Lis-López0Cristina Bauset1Marta Seco-Cervera2Dulce Macias-Ceja3Francisco Navarro4Ángeles Álvarez5Juan Vicente Esplugues6Sara Calatayud7Maria Dolores Barrachina8Dolores Ortiz-Masià9Jesús Cosín-Roger10Departamento de Farmacología, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, SpainDepartamento de Farmacología, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, SpainFISABIO (Fundación para el Fomento de la Investigación Sanitaria y Biomédica), Hospital Dr. Peset, 46017 Valencia, SpainDepartamento de Farmacología, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, SpainServicio Cirugía y Coloproctología, Hospital de Manises, 46940 Valencia, SpainDepartamento de Farmacología, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, SpainDepartamento de Farmacología, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, SpainDepartamento de Farmacología, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, SpainDepartamento de Farmacología, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, SpainCIBERehd (Centro de Investigaciones en Red Enfermedad Hepática y Digestiva), 28029 Madrid, SpainDepartamento de Farmacología, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, SpainIntestinal fibrosis is a common complication that affects more than 50% of Crohn´s Disease (CD) patients. 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-β. 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-β treatment. P2X7 regulates collagen expression in human intestinal fibroblasts, while the lack of this receptor aggravates intestinal fibrosis.https://www.mdpi.com/1422-0067/24/16/12936P2X7 receptorintestinal fibrosisfibroblastsCrohn’s Disease |
| spellingShingle | Lluis Lis-López Cristina Bauset Marta Seco-Cervera Dulce Macias-Ceja Francisco Navarro Ángeles Álvarez Juan Vicente Esplugues Sara Calatayud Maria Dolores Barrachina Dolores Ortiz-Masià Jesús Cosín-Roger P2X7 Receptor Regulates Collagen Expression in Human Intestinal Fibroblasts: Relevance in Intestinal Fibrosis International Journal of Molecular Sciences P2X7 receptor intestinal fibrosis fibroblasts Crohn’s Disease |
| title | P2X7 Receptor Regulates Collagen Expression in Human Intestinal Fibroblasts: Relevance in Intestinal Fibrosis |
| title_full | P2X7 Receptor Regulates Collagen Expression in Human Intestinal Fibroblasts: Relevance in Intestinal Fibrosis |
| title_fullStr | P2X7 Receptor Regulates Collagen Expression in Human Intestinal Fibroblasts: Relevance in Intestinal Fibrosis |
| title_full_unstemmed | P2X7 Receptor Regulates Collagen Expression in Human Intestinal Fibroblasts: Relevance in Intestinal Fibrosis |
| title_short | P2X7 Receptor Regulates Collagen Expression in Human Intestinal Fibroblasts: Relevance in Intestinal Fibrosis |
| title_sort | p2x7 receptor regulates collagen expression in human intestinal fibroblasts relevance in intestinal fibrosis |
| topic | P2X7 receptor intestinal fibrosis fibroblasts Crohn’s Disease |
| url | https://www.mdpi.com/1422-0067/24/16/12936 |
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