Gene Expression Profiling of Mediators Associated with the Inflammatory Pathways in the Intestinal Tissue from Patients with Ulcerative Colitis

الملخص EN

Background.

Multiple genes have been associated with IBD, and many of these can be linked to alterations in autophagy, UPR, ubiquitination, and metabolic and immune response pathways.

The aim of this study was to analyze a transcriptomic panel of mediators associated with the inflammatory pathways in the colonic mucosa of UC patients.

Patients and Methods.

We studied a total of 100 patients with definitive diagnosis of UC (50 active and 50 in remission) and a control group (50 subjects) without endoscopic evidence of intestinal inflammation.

Colonic mucosal biopsies were taken by colonoscopy and preserved in RNA later.

Gene expression were measured by real-time polymerase chain reaction (RT-PCR).

Results.

The gene expressions of XBP1, AGR2, HSPA5, UBE2L3, TNFRSF14, LAMP3, FCGR2A, LSP1, CTLA4, SOD2, TDO2, and ALDOB mRNA levels were significantly higher in the colonic mucosa from UC patients (both quiescent and active) as compared to the control group (P<0.05).

Conversely, IRGM, ORDML3, UBD, CUL2, CYLD, FOXC2, FOXO4, DOK3, and SNX20 mRNA levels were found to be significantly lower in patients with active disease, as compared to those with active disease (P<0.05).

Gene expressions of IRGM, CTLA4, FOXO4, SLC26A3, SLC39A4, SOD2, TDO2, and ALDOB were associated with clinical outcomes, such as medical treatment in response to aminosalicylates, histological remission, clinical course, and evolution.

Conclusions: The gene expressions of FOXO4, ALDOB, SOD2, TOD2, SLC26A3, and SLC39A4 were associated with the clinical course and histological activity and are of relevance since these provide the utility of new prognostic markers in IBD.

Gene expression signature showed dysregulation in mediators associated with autophagy, ubiquitination, ER stress, oxidative stress, carbohydrate metabolism, solute transport, and T cell regulation in the colonic mucosa from patients with UC, suggesting that these genes could be involved in the pathogenesis of UC.