Gene Expression Profiling of Mediators Associated with the Inflammatory Pathways in the Intestinal Tissue from...

Area of Science:

• Gastroenterology and Hepatology
• Molecular Biology
• Immunology

Background:

• Ulcerative colitis (UC) pathogenesis involves multiple genes linked to autophagy, UPR, ubiquitination, and immune/metabolic pathways.
• Understanding transcriptomic alterations in UC colonic mucosa is crucial for identifying disease mechanisms.

Purpose of the Study:

• To analyze a transcriptomic panel of mediators in the colonic mucosa of UC patients.
• To identify gene expression patterns associated with UC activity and clinical outcomes.

Main Methods:

• Gene expression analysis using real-time polymerase chain reaction (RT-PCR).
• Study included 100 UC patients (50 active, 50 remission) and 50 controls.
• Colonic mucosal biopsies were collected via colonoscopy.

Main Results:

• Elevated mRNA levels of XBP1, AGR2, HSPA5, UBE2L3, TNFRSF14, LAMP3, FCGR2A, LSP1, CTLA4, SOD2, TDO2, and ALDOB in UC patients compared to controls.
• Lower mRNA levels of IRGM, ORDML3, UBD, CUL2, CYLD, FOXC2, FOXO4, DOK3, and SNX20 in active UC patients versus those in remission.
• Specific gene expressions (IRGM, CTLA4, FOXO4, SLC26A3, SLC39A4, SOD2, TDO2, ALDOB) correlated with clinical outcomes like treatment response and remission.

Conclusions:

• Gene expressions of FOXO4, ALDOB, SOD2, TOD2, SLC26A3, and SLC39A4 are linked to clinical course and histological activity, suggesting their utility as prognostic markers in IBD.
• Dysregulated gene expression in UC colonic mucosa involves pathways of autophagy, ubiquitination, ER stress, oxidative stress, metabolism, and T cell regulation.
• These identified genes may play a significant role in the pathogenesis of UC.