Exploration of JAK/STAT pathway activation in ulcerative colitis reveals sex-dependent activation of JAK2/STAT3 in the inflammatory response
IntroductionUlcerative 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.MethodsWe conducted a prospective, observ...
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2025-07-01
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| author | Cristina Calviño-Suárez Cristina Calviño-Suárez Mariña Durán-Rubí Mariña Durán-Rubí José Brea José Brea David Moreira David Moreira Inés Ardao Inés Ardao Iria Brocos-Mosquera Rocío Ferreiro-Iglesias Rocío Ferreiro-Iglesias Sol Porto-Silva Sol Porto-Silva Laura Nieto-Garcia Laura Nieto-Garcia María José Varela María Isabel Loza María Isabel Loza María Isabel Loza Antón L. Martínez Antón L. Martínez Manuel Barreiro-de Acosta Manuel Barreiro-de Acosta |
| author_facet | Cristina Calviño-Suárez Cristina Calviño-Suárez Mariña Durán-Rubí Mariña Durán-Rubí José Brea José Brea David Moreira David Moreira Inés Ardao Inés Ardao Iria Brocos-Mosquera Rocío Ferreiro-Iglesias Rocío Ferreiro-Iglesias Sol Porto-Silva Sol Porto-Silva Laura Nieto-Garcia Laura Nieto-Garcia María José Varela María Isabel Loza María Isabel Loza María Isabel Loza Antón L. Martínez Antón L. Martínez Manuel Barreiro-de Acosta Manuel Barreiro-de Acosta |
| author_sort | Cristina Calviño-Suárez |
| collection | DOAJ |
| description | IntroductionUlcerative 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.MethodsWe 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.ResultsInflamed 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).DiscussionThese 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. |
| format | Article |
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| institution | Kabale University |
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| publishDate | 2025-07-01 |
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| spelling | doaj-art-c6b68f47f3ec41af896931b5c23ce08c2025-08-20T03:51:07ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.16097401609740Exploration of JAK/STAT pathway activation in ulcerative colitis reveals sex-dependent activation of JAK2/STAT3 in the inflammatory responseCristina Calviño-Suárez0Cristina Calviño-Suárez1Mariña Durán-Rubí2Mariña Durán-Rubí3José Brea4José Brea5David Moreira6David Moreira7Inés Ardao8Inés Ardao9Iria Brocos-Mosquera10Rocío Ferreiro-Iglesias11Rocío Ferreiro-Iglesias12Sol Porto-Silva13Sol Porto-Silva14Laura Nieto-Garcia15Laura Nieto-Garcia16María José Varela17María Isabel Loza18María Isabel Loza19María Isabel Loza20Antón L. Martínez21Antón L. Martínez22Manuel Barreiro-de Acosta23Manuel Barreiro-de Acosta24Department of Gastroenterology and Hepatology, University Hospital of Santiago De Compostela, Santiago de Compostela, SpainInstituto de Investigacións Sanitarias de Santiago de Compostela (IDIS), Santiago de Compostela, SpainInstituto de Investigacións Sanitarias de Santiago de Compostela (IDIS), Santiago de Compostela, SpainInnopharma Drug Screening and Pharmacogenomics Platform, BioFarma Research Group, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Department of Pharmacology, Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela, Santiago de Compostela, SpainInstituto de Investigacións Sanitarias de Santiago de Compostela (IDIS), Santiago de Compostela, SpainInnopharma Drug Screening and Pharmacogenomics Platform, BioFarma Research Group, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Department of Pharmacology, Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela, Santiago de Compostela, SpainInnopharma Drug Screening and Pharmacogenomics Platform, BioFarma Research Group, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Department of Pharmacology, Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela, Santiago de Compostela, SpainKaertor Foundation, Santiago de Compostela, SpainInnopharma Drug Screening and Pharmacogenomics Platform, BioFarma Research Group, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Department of Pharmacology, Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela, Santiago de Compostela, SpainKaertor Foundation, Santiago de Compostela, SpainInnopharma Drug Screening and Pharmacogenomics Platform, BioFarma Research Group, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Department of Pharmacology, Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela, Santiago de Compostela, SpainDepartment of Gastroenterology and Hepatology, University Hospital of Santiago De Compostela, Santiago de Compostela, SpainInstituto de Investigacións Sanitarias de Santiago de Compostela (IDIS), Santiago de Compostela, SpainDepartment of Gastroenterology and Hepatology, University Hospital of Santiago De Compostela, Santiago de Compostela, SpainInstituto de Investigacións Sanitarias de Santiago de Compostela (IDIS), Santiago de Compostela, SpainDepartment of Gastroenterology and Hepatology, University Hospital of Santiago De Compostela, Santiago de Compostela, SpainInstituto de Investigacións Sanitarias de Santiago de Compostela (IDIS), Santiago de Compostela, SpainInnopharma Drug Screening and Pharmacogenomics Platform, BioFarma Research Group, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Department of Pharmacology, Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela, Santiago de Compostela, SpainInstituto de Investigacións Sanitarias de Santiago de Compostela (IDIS), Santiago de Compostela, SpainInnopharma Drug Screening and Pharmacogenomics Platform, BioFarma Research Group, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Department of Pharmacology, Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela, Santiago de Compostela, SpainKaertor Foundation, Santiago de Compostela, SpainInstituto de Investigacións Sanitarias de Santiago de Compostela (IDIS), Santiago de Compostela, SpainInnopharma Drug Screening and Pharmacogenomics Platform, BioFarma Research Group, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Department of Pharmacology, Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela, Santiago de Compostela, SpainDepartment of Gastroenterology and Hepatology, University Hospital of Santiago De Compostela, Santiago de Compostela, SpainInstituto de Investigacións Sanitarias de Santiago de Compostela (IDIS), Santiago de Compostela, SpainIntroductionUlcerative 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.MethodsWe 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.ResultsInflamed 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).DiscussionThese 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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1609740/fullulcerative colitisJAK/STAT pathwayphosphorylationsex-specific differencesinflammatory signalingpersonalized therapy |
| spellingShingle | Cristina Calviño-Suárez Cristina Calviño-Suárez Mariña Durán-Rubí Mariña Durán-Rubí José Brea José Brea David Moreira David Moreira Inés Ardao Inés Ardao Iria Brocos-Mosquera Rocío Ferreiro-Iglesias Rocío Ferreiro-Iglesias Sol Porto-Silva Sol Porto-Silva Laura Nieto-Garcia Laura Nieto-Garcia María José Varela María Isabel Loza María Isabel Loza María Isabel Loza Antón L. Martínez Antón L. Martínez Manuel Barreiro-de Acosta Manuel Barreiro-de Acosta Exploration of JAK/STAT pathway activation in ulcerative colitis reveals sex-dependent activation of JAK2/STAT3 in the inflammatory response Frontiers in Immunology ulcerative colitis JAK/STAT pathway phosphorylation sex-specific differences inflammatory signaling personalized therapy |
| title | 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_short | 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 |
| topic | ulcerative colitis JAK/STAT pathway phosphorylation sex-specific differences inflammatory signaling personalized therapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1609740/full |
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