Exploration of JAK/STAT pathway activation in ulcerative colitis reveals sex-dependent activation of JAK2/STAT3 in the inflammatory response

Introduction. Ulcerative colitis (UC) is characterized by aberrant immune responses involving multiple inflammatory pathways, including JAK/STAT signaling. However, the specific roles and interactions of individual components within this pathway remain unclear. Methods. We conducted a prospective, o...

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Authors: Calviño-Suárez, Cristina, Durán Rubí, Mariña, Brea Floriani, José Manuel, Moreira Álvarez, David, Ardao Palacios, Inés, Brocos Mosquera, Iria, Ferreiro Iglesias, Rocío, Porto Silva, Sol, Nieto-García, Laura, Varela Liste, María José, Loza García, María Isabel, Martínez Rodríguez, Antón Leandro, Barreiro de Acosta, Manuel
Format: article
Publication Date:2025
Country:España
Institution:Universidad de Santiago de Compostela (USC)
Repository:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
Language:English
OAI Identifier:oai:minerva.usc.gal:10347/42564
Online Access:https://hdl.handle.net/10347/42564
Access Level:Open access
Keyword:Ulcerative colitis
JAK/STAT pathway
Phosphorylation
Sex-specific differences
Inflammatory signaling
Personalized therapy
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spelling Exploration of JAK/STAT pathway activation in ulcerative colitis reveals sex-dependent activation of JAK2/STAT3 in the inflammatory responseCalviño-Suárez, CristinaDurán Rubí, MariñaBrea Floriani, José ManuelMoreira Álvarez, DavidArdao Palacios, InésBrocos Mosquera, IriaFerreiro Iglesias, RocíoPorto Silva, SolNieto-García, LauraVarela Liste, María JoséLoza García, María IsabelMartínez Rodríguez, Antón LeandroBarreiro de Acosta, ManuelUlcerative colitisJAK/STAT pathwayPhosphorylationSex-specific differencesInflammatory signalingPersonalized therapyIntroduction. Ulcerative colitis (UC) is characterized by aberrant immune responses involving multiple inflammatory pathways, including JAK/STAT signaling. However, the specific roles and interactions of individual components within this pathway remain unclear. Methods. We conducted a prospective, observational, single-center study enrolling 61 adult UC patients undergoing routine colonoscopy with endoscopic activity (Mayo Endoscopic Score > 0). Paired biopsies from inflamed and non-inflamed colonic mucosa were collected. Phosphorylation levels of JAK1, JAK2, JAK3, TYK2, STAT1, STAT3, and STAT4 were quantified by Western blot. Results. Inflamed tissue showed significantly increased phosphorylation of JAK2, JAK3, TYK2, STAT1, STAT3, and STAT4 compared to non-inflamed mucosa (p < 0.05), while JAK1 levels did not differ significantly. Correlation analysis revealed coordinated activation among JAK2, JAK3, TYK2, and STAT3, suggesting interdependent roles. Notably, male patients exhibited significantly higher activation of JAK2 and STAT3 than female patients (p < 0.05). Discussion. These findings highlight a heterogeneous but important involvement of the JAK/STAT pathway in UC pathophysiology. The observed sex-specific differences and coordinated activation patterns suggest the value of personalized therapeutic approaches targeting specific components of this pathway.FrontiersUniversidade de Santiago de Compostela. Centro de Investigación en Medicina Molecular e Enfermidades Crónicas (CiMUS)20252025-07-2120252025-07-21journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10347/42564reponame:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostelainstname:Universidad de Santiago de Compostela (USC)InglésengAgencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023 CPP2021-009055 Inhibidores No-sistemicos JAK para tratamientos más seguros en CU y ECopen accesshttp://purl.org/coar/access_right/c_abf2© 2025 Calviño-Suarez, Duran-Rubi, Brea, Moreira, Ardao, Brocos-Mosquera, Ferreiro-Iglesias, Porto-Silva, Nieto-Garcia, Varela, Loza, Martinez and Barreiro-de Acosta. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:minerva.usc.gal:10347/425642026-06-15T12:47:27Z
dc.title.none.fl_str_mv Exploration of JAK/STAT pathway activation in ulcerative colitis reveals sex-dependent activation of JAK2/STAT3 in the inflammatory response
title Exploration of JAK/STAT pathway activation in ulcerative colitis reveals sex-dependent activation of JAK2/STAT3 in the inflammatory response
spellingShingle Exploration of JAK/STAT pathway activation in ulcerative colitis reveals sex-dependent activation of JAK2/STAT3 in the inflammatory response
Calviño-Suárez, Cristina
Ulcerative colitis
JAK/STAT pathway
Phosphorylation
Sex-specific differences
Inflammatory signaling
Personalized therapy
title_short Exploration of JAK/STAT pathway activation in ulcerative colitis reveals sex-dependent activation of JAK2/STAT3 in the inflammatory response
title_full Exploration of JAK/STAT pathway activation in ulcerative colitis reveals sex-dependent activation of JAK2/STAT3 in the inflammatory response
title_fullStr Exploration of JAK/STAT pathway activation in ulcerative colitis reveals sex-dependent activation of JAK2/STAT3 in the inflammatory response
title_full_unstemmed Exploration of JAK/STAT pathway activation in ulcerative colitis reveals sex-dependent activation of JAK2/STAT3 in the inflammatory response
title_sort Exploration of JAK/STAT pathway activation in ulcerative colitis reveals sex-dependent activation of JAK2/STAT3 in the inflammatory response
dc.creator.none.fl_str_mv Calviño-Suárez, Cristina
Durán Rubí, Mariña
Brea Floriani, José Manuel
Moreira Álvarez, David
Ardao Palacios, Inés
Brocos Mosquera, Iria
Ferreiro Iglesias, Rocío
Porto Silva, Sol
Nieto-García, Laura
Varela Liste, María José
Loza García, María Isabel
Martínez Rodríguez, Antón Leandro
Barreiro de Acosta, Manuel
author Calviño-Suárez, Cristina
author_facet Calviño-Suárez, Cristina
Durán Rubí, Mariña
Brea Floriani, José Manuel
Moreira Álvarez, David
Ardao Palacios, Inés
Brocos Mosquera, Iria
Ferreiro Iglesias, Rocío
Porto Silva, Sol
Nieto-García, Laura
Varela Liste, María José
Loza García, María Isabel
Martínez Rodríguez, Antón Leandro
Barreiro de Acosta, Manuel
author_role author
author2 Durán Rubí, Mariña
Brea Floriani, José Manuel
Moreira Álvarez, David
Ardao Palacios, Inés
Brocos Mosquera, Iria
Ferreiro Iglesias, Rocío
Porto Silva, Sol
Nieto-García, Laura
Varela Liste, María José
Loza García, María Isabel
Martínez Rodríguez, Antón Leandro
Barreiro de Acosta, Manuel
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade de Santiago de Compostela. Centro de Investigación en Medicina Molecular e Enfermidades Crónicas (CiMUS)
dc.subject.none.fl_str_mv Ulcerative colitis
JAK/STAT pathway
Phosphorylation
Sex-specific differences
Inflammatory signaling
Personalized therapy
topic Ulcerative colitis
JAK/STAT pathway
Phosphorylation
Sex-specific differences
Inflammatory signaling
Personalized therapy
description Introduction. Ulcerative colitis (UC) is characterized by aberrant immune responses involving multiple inflammatory pathways, including JAK/STAT signaling. However, the specific roles and interactions of individual components within this pathway remain unclear. Methods. We conducted a prospective, observational, single-center study enrolling 61 adult UC patients undergoing routine colonoscopy with endoscopic activity (Mayo Endoscopic Score > 0). Paired biopsies from inflamed and non-inflamed colonic mucosa were collected. Phosphorylation levels of JAK1, JAK2, JAK3, TYK2, STAT1, STAT3, and STAT4 were quantified by Western blot. Results. Inflamed tissue showed significantly increased phosphorylation of JAK2, JAK3, TYK2, STAT1, STAT3, and STAT4 compared to non-inflamed mucosa (p < 0.05), while JAK1 levels did not differ significantly. Correlation analysis revealed coordinated activation among JAK2, JAK3, TYK2, and STAT3, suggesting interdependent roles. Notably, male patients exhibited significantly higher activation of JAK2 and STAT3 than female patients (p < 0.05). Discussion. These findings highlight a heterogeneous but important involvement of the JAK/STAT pathway in UC pathophysiology. The observed sex-specific differences and coordinated activation patterns suggest the value of personalized therapeutic approaches targeting specific components of this pathway.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025-07-21
2025
2025-07-21
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10347/42564
url https://hdl.handle.net/10347/42564
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Agencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023 CPP2021-009055 Inhibidores No-sistemicos JAK para tratamientos más seguros en CU y EC
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers
publisher.none.fl_str_mv Frontiers
dc.source.none.fl_str_mv reponame:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
instname:Universidad de Santiago de Compostela (USC)
instname_str Universidad de Santiago de Compostela (USC)
reponame_str Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
collection Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
repository.name.fl_str_mv
repository.mail.fl_str_mv
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