ORIGINAL RESEARCH article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1609740
This article is part of the Research TopicBiomarkers and Beyond: Predicting Course and Tailoring Treatment in Inflammatory Bowel DiseasesView all 13 articles
Exploration of JAK/SAT pathway activation in ulcerative colitis reveals a sex-dependence activation of JAK2/STAT3 in inflammatory response
Provisionally accepted
Cristina Calviño-Suárez1,2
Mariña Durán-Rubí2,3
José Brea-Floriani2,3
David Moreira-Álvarez3,4
Inés Ardao-Palacios3,4
Iria Brocos-Mosquera3
Rocio Ferreiro-Iglesias1,2
Sol Porto-Silva1,2
Laura Nieto-García1,2
María José Varela-Liste3
Maria Isabel Loza-García2,3,4
Antón Leandro Martínez-Rodríguez2,3*
Manuel Barreiro-de Acosta1,2*- 1Department of Gastroenterology and Hepatology, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain
- 2Instituto de Investigacións Sanitarias de Santiago de Compostela (IDIS), Santiago de Compostela, Spain
- 3BioFarma research group. CiMUS. Department of Pharmacology, Pharmacy and Pharmaceutical Technology. Faculty of Pharmacy. University of Santiago de Compostela, Santiago de Compostela, Spain
- 4Kaertor Foundation, Santiago de Compostela, Galicia, Spain
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Ulcerative colitis (UC) is characterized by aberrant immune responses involving various inflammatory pathways, including JAK/STAT signaling, but the specific roles of individual pathway components remain unclear. We aimed to profile the activation of the JAK/STAT pathway in colonic biopsies from UC patients and identify potential correlations and sex-specific differences. In a prospective, observational, single-center study, we enrolled sixty-one adult UC patients undergoing routine colonoscopy who had any degree of endoscopic activity (Mayo Endoscopic Score > 0). Paired biopsies from inflamed and non-inflamed mucosa were analyzed by Western blot to quantify phosphorylation levels of JAK1, JAK2, JAK3, TYK2, STAT1, STAT3, and STAT4. We found significantly higher phosphorylation of JAK2, JAK3, TYK2, STAT1, STAT3, and STAT4 in inflamed versus noninflamed areas (p<0.05), whereas JAK1 showed no significant difference. Correlation analysis revealed coordinated activation among JAK2, JAK3, TYK2, and STAT3, suggesting interdependent roles. Notably, male patients exhibited significantly higher JAK2 and STAT3 activation compared to females (p<0.05). These findings highlight the important yet heterogeneous role of JAK/STAT signaling in UC pathophysiology, underscoring the potential for personalized treatment approaches that account for individual pathway activation profiles and sex-specific differences.
Keywords: ulcerative colitis, JAK/STAT pathway, Phosphorylation, Sex-specific differences, inflammatory signaling, personalized therapy
Received: 10 Apr 2025; Accepted: 25 Jun 2025.
Copyright: © 2025 Calviño-Suárez, Durán-Rubí, Brea-Floriani, Moreira-Álvarez, Ardao-Palacios, Brocos-Mosquera, Ferreiro-Iglesias, Porto-Silva, Nieto-García, Varela-Liste, Loza-García, Martínez-Rodríguez 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) or licensor 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.
* Correspondence:
Antón Leandro Martínez-Rodríguez, Instituto de Investigacións Sanitarias de Santiago de Compostela (IDIS), Santiago de Compostela, Spain
Manuel Barreiro-de Acosta, Department of Gastroenterology and Hepatology, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain
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