Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by an excessive and dysregulated immune response in the intestinal mucosa. Among the intracellular signaling mechanisms implicated in this process, the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway plays a central role in mediating cytokine signaling and modulating inflammation. Despite the clinical use of JAK inhibitors, the precise contribution of individual JAK and STAT proteins to the inflammatory response in UC remains incompletely understood.
This study aimed to characterize the activation profile of the JAK/STAT pathway in colonic biopsies from patients with active UC and to explore possible differences related to patient sex. Sixty-one adult UC patients with endoscopic activity (Mayo Endoscopic Score > 0) undergoing routine colonoscopy were prospectively enrolled. Paired biopsies were collected from inflamed and non-inflamed mucosal areas. Protein extracts were analyzed by Western blot to quantify the phosphorylated forms of JAK1, JAK2, JAK3, TYK2, STAT1, STAT3, and STAT4, using β-actin as a loading control.
Phosphorylation of JAK2, JAK3, TYK2, STAT1, STAT3, and STAT4 was significantly increased in inflamed tissue compared with non-inflamed regions, reflecting enhanced pathway activation.Correlation analysis revealed coordinated activation patterns among JAK2, JAK3, TYK2, and STAT3. Notably, JAK2 and STAT3 phosphorylation levels were significantly higher in male patients, indicating sex-dependent differences in pathway modulation. In contrast, JAK1 did not show differential activation under any condition.
In summary, these findings provide an integrated overview of JAK/STAT signaling dynamics in UC, revealing a selective and coordinated activation of specific pathway components in inflamed mucosa. The observed trends suggest that biological sex may influence JAK/STAT signaling, and further study of this pathway could help to understand its potential implications for individualized therapeutic approaches in ulcerative colitis and other inflammatory disorders.
