{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:12:19Z","timestamp":1792033939413,"version":"4.4.0"},"reference-count":47,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CONACyT-Mexico Grant Ciencia de Frontera","award":["2020-552265"],"award-info":[{"award-number":["2020-552265"]}]},{"name":"SECIHTI Ciencia B\u00e1sica y de Frontera","award":["CBF-2025-G-145"],"award-info":[{"award-number":["CBF-2025-G-145"]}]},{"DOI":"10.13039\/100016991","name":"Universidad de Guadalajara","doi-asserted-by":"publisher","award":["PIN-2025"],"award-info":[{"award-number":["PIN-2025"]}],"id":[{"id":"10.13039\/100016991","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Multiple sclerosis (MS), the most prevalent chronic inflammatory, demyelinating and neurodegenerative disease of the central nervous system in young adults, exhibits marked sexual dimorphism, with a 3:1 female-to-male ratio, but more severe symptoms and greater neurological damage in males. Increasing attention has focused on identifying circulating molecules that reflect inflammatory activity within the central nervous system and could clarify the mechanisms underlying MS. Pleiotrophin (PTN), a cytokine implicated in autoimmune and neurological diseases, is significantly elevated in patients with relapsing-remitting MS (RRMS). To explore the potential contribution of PTN and its receptors to neuroinflammatory signaling, we quantified the mRNA expression of PTN receptors in peripheral blood mononuclear cells from RRMS patients compared to untreated RRMS patients and healthy control subjects. We further performed an in silico molecular docking and molecular dynamics analysis to assess the possible functional significance of PTN-receptor interactions. Our results show a significant overexpression of integrin subunit beta-3 (ITGB3) mRNA in peripheral blood mononuclear cells from RRMS patients compared to healthy control subjects. Molecular docking shows that PTN could binds to the metal ion-dependent adhesion site domain of ITGB3 via Mg2+\/Ca2+-mediated stabilization and has a higher binding affinity than fibrinogen, the canonical endogenous ligand. These findings suggest that ITGB3 could be a dynamically regulated integrin receptor in RRMS that may participate in PTN-driven neuroinflammatory pathways in peripheral blood immune cells, influenced by disease stage, sex, and immunotherapy. While our results support the biological plausibility of PTN\u2013ITGB3 engagement, they remain hypothesis-generating and require functional validation. The integration of molecular expression data and computational modeling underscores the potential involvement of ITGB3 as a possible participant in MS and warrants further investigation of its clinical and mechanistic role.<\/jats:p>","DOI":"10.3390\/ijms262412094","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T12:47:26Z","timestamp":1765889246000},"page":"12094","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Overexpression of ITGB3 in Peripheral Blood Mononuclear Cells of Relapsing-Remitting Multiple Sclerosis Patients"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2322-3111","authenticated-orcid":false,"given":"Giselle Berenice Vela","family":"Sancho","sequence":"first","affiliation":[{"name":"Laboratorio de Neuroinmunobiolog\u00eda Molecular, Instituto de Neurociencias Translacionales, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo E.","family":"Buendia-Corona","sequence":"additional","affiliation":[{"name":"Department of Chemical Biological Sciences, Universidad de las Am\u00e9ricas Puebla, Puebla 72810, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8856-8722","authenticated-orcid":false,"given":"Mar\u00eda Paulina","family":"Reyes-Mata","sequence":"additional","affiliation":[{"name":"Departamento de Disciplinas Filos\u00f3fico, Metodol\u00f3gicas e Instrumentales, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8321-7883","authenticated-orcid":false,"given":"Mario Alberto","family":"Mireles-Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Unidad M\u00e9dica de Alta Especialidad (UMAE), Hospital de Especialidades (HE), Centro M\u00e9dico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5424-9130","authenticated-orcid":false,"given":"Christian","family":"Gri\u00f1\u00e1n-Ferr\u00e9","sequence":"additional","affiliation":[{"name":"Pharmacology Section, Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, Institute of Neuroscience, Universitat de Barcelona, 08028 Barcelona, Spain"},{"name":"CiberNed, Network Center for Neurodegenerative Diseases, National Spanish Health Institute Carlos III, 28220 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3095-4254","authenticated-orcid":false,"given":"Merc\u00e8","family":"Pall\u00e0s","sequence":"additional","affiliation":[{"name":"Pharmacology Section, Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, Institute of Neuroscience, Universitat de Barcelona, 08028 Barcelona, Spain"},{"name":"CiberNed, Network Center for Neurodegenerative Diseases, National Spanish Health Institute Carlos III, 28220 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5662-9076","authenticated-orcid":false,"given":"Ana Laura","family":"M\u00e1rquez-Aguirre","sequence":"additional","affiliation":[{"name":"Unidad de Biotecnolog\u00eda M\u00e9dica y Farmac\u00e9utica, Centro de Investigaci\u00f3n y Asistencia en Tecnolog\u00eda y Dise\u00f1o del Estado de Jalisco A.C. (CIATEJ), Guadalajara 44270, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6067-6868","authenticated-orcid":false,"given":"Lenin","family":"Pavon","sequence":"additional","affiliation":[{"name":"Laboratorio de Psicoinmunolog\u00eda, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz, Mexico City 14370, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9982-7571","authenticated-orcid":false,"given":"Oscar","family":"Arias-Carri\u00f3n","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Neurociencias, Cl\u00ednica, Instituto Nacional de Rehabilitaci\u00f3n Luis Guillermo Ibarra Ibarra, Mexico City 14389, Mexico"},{"name":"Escuela de Medicina y Ciencias de la Salud, Tecnologico de Monterrey, Mexico City 14380, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7039-6184","authenticated-orcid":false,"given":"Jos\u00e9 de Jes\u00fas","family":"Guerrero-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Banco Central de Sangre, Unidad M\u00e9dica de Alta Especialidad (UMAE), Hospital de Especialidades (HE), Centro M\u00e9dico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44340, Mexico"},{"name":"Departamento de Farmacobiolog\u00eda, Centro Universitario de Ciencias Exactas e Ingenier\u00edas (CUCEI), Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7443-2514","authenticated-orcid":false,"given":"Daniel","family":"Ortu\u00f1o-Sahag\u00fan","sequence":"additional","affiliation":[{"name":"Laboratorio de Neuroinmunobiolog\u00eda Molecular, Instituto de Neurociencias Translacionales, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1177\/1352458517694432","article-title":"New insights into the burden and costs of multiple sclerosis in Europe","volume":"23","author":"Kobelt","year":"2017","journal-title":"Mult. 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