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P039 New molecular markers of the development of ulcerative colitis

Iakovlev, A.A.(1);Volkov, A.(2);Tarasova, G.(2);Zubova, A.(2);

(1)Rostov State Medical University, Department of Gastroenterology, Rostov-on-Don, Russian Federation;(2)Rostov State Medical University, Gastroenterology, Rostov-on-Don, Russian Federation

Background

The mechanisms of ulcerative colitis (UC) progression require detailed study. Modern achievements of proteomic methods of analysis are ideal for research that is free from hypotheses and allows us to define molecular characteristics of inflammation in colon mucosa of UC patients.

Methods

The study was comparative cohort with parallel design and included 88 patients (range from 22 to 35 years, 37 men and 51 women): 53 (60.2%) pancolitis and 35 (39.8%) left-sided UC, mild and moderate activity. The control group included 30 healthy individuals. Biosamples of colon mucosa in patients with UC in the active stage and in healthy persons were received by ileocolonoscopy with colon mucosa biopsy. The separation of individual proteins of colon mucosa was based on technologies of IEF, SDS-PAGE, 2DPAGE, by standard sets (MB-HIC C8 Kit, MB-IMAC Cu, MB-Wax Kit, «Bruker», USA). Automated mass spectrometry imaging was performed by MALDI-TOF-MS/MS, Ultraflex II, «Bruker», USA). The data of the molecular interactions and functional features of proteins were received with STRING 10.0 database.

Results

We identified following functional groups of peptides and proteins in molecular patterns  of colon mucosa in UC patients: SMAD family member 2 (SMAD2) activates the transcription of TFG1β, that leads to specific regulation of the CCN2 gene in cells and the development of fibrosis in colon submucosa in UC patients; the stimulation of the expression of apoС-III in affected colon mucosa in UC is associated with the activation of the FOXO1 signaling pathway that supports inflammatory processes in colon mucosa; the second small heat shock protein (HSP2) controls the apoptosis of colonocytes, is also responsible for the mucosa resistance to therapeutic strategies; caspase 8 protects colonocytes from TNFα-induced cell death through a necroptosis mechanism via the blockade of the RIP3 expression; the expression of prohibitin maintains optimal activity of the electronic transport chain through the activity of transcription factor STAT3 and the decrease in the TNFα expression; significant decrease of the PPARγ expression promotes the activation of STAT and AP-1 signaling pathways, which promotes the activity of immune and inflamation processes in colon mucosa and a significant increase in the NF-kB expression in colon mucosa is associated with the activation of TNFα and IL-1, which promotes the increase of immune processes in colon mucosa.

Conclusion

Bioinformatics analysis revealed the presence of molecules that are the participants in the universal pathways of UC in the active stage, and the molecular interactions involved. This information may provide new avenues for the development of novel diagnostic tests for UC.

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