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溃疡性结肠炎中JAK/STAT信号通路激活的研究揭示了炎症反应中JAK2/STAT3的性别依赖性激活。

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

作者信息

Calviño-Suárez Cristina, Durán-Rubí Mariña, Brea José, Moreira David, Ardao Inés, Brocos-Mosquera Iria, Ferreiro-Iglesias Rocío, Porto-Silva Sol, Nieto-Garcia Laura, Varela María José, Loza María Isabel, Martínez Antón L, Barreiro-de Acosta Manuel

机构信息

Department of Gastroenterology and Hepatology, University Hospital of Santiago De Compostela, Santiago de Compostela, Spain.

Instituto de Investigacións Sanitarias de Santiago de Compostela (IDIS), Santiago de Compostela, Spain.

出版信息

Front Immunol. 2025 Jul 21;16:1609740. doi: 10.3389/fimmu.2025.1609740. eCollection 2025.

DOI:10.3389/fimmu.2025.1609740
PMID:40761789
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12318950/
Abstract

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.

摘要

引言

溃疡性结肠炎（UC）的特征是涉及多种炎症途径的异常免疫反应，包括JAK/STAT信号通路。然而，该通路中各个组件的具体作用和相互作用仍不清楚。

方法

我们进行了一项前瞻性、观察性、单中心研究，纳入了61例接受常规结肠镜检查且具有内镜活动度（梅奥内镜评分>0）的成年UC患者。采集了发炎和未发炎结肠黏膜的配对活检组织。通过蛋白质免疫印迹法对JAK1、JAK2、JAK3、TYK2、STAT1、STAT3和STAT4的磷酸化水平进行定量。

结果

与未发炎的黏膜相比，发炎组织中JAK2、JAK3、TYK2、STAT1、STAT3和STAT4的磷酸化水平显著升高（p<0.05），而JAK1水平无显著差异。相关性分析显示JAK2、JAK3、TYK2和STAT3之间存在协同激活，提示它们具有相互依赖的作用。值得注意的是，男性患者JAK2和STAT3的激活水平显著高于女性患者（p<0.05）。

讨论

这些发现突出了JAK/STAT通路在UC病理生理学中存在异质性但重要的参与情况。观察到的性别特异性差异和协同激活模式表明针对该通路特定组件的个性化治疗方法具有价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6639/12318950/0f51a9c7ece2/fimmu-16-1609740-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6639/12318950/d50e681db7c4/fimmu-16-1609740-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6639/12318950/52ae60107637/fimmu-16-1609740-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6639/12318950/3a0c36f55269/fimmu-16-1609740-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6639/12318950/0f51a9c7ece2/fimmu-16-1609740-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6639/12318950/d50e681db7c4/fimmu-16-1609740-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6639/12318950/52ae60107637/fimmu-16-1609740-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6639/12318950/3a0c36f55269/fimmu-16-1609740-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6639/12318950/0f51a9c7ece2/fimmu-16-1609740-g004.jpg

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