AKAP12/Gravin is over-expressed in patients with ulcerative colitis.

The gene of A-kinase anchor protein 12 (AKAP12) regulates cell cycle progression, cell motility, and morphology through its multiple scaffolding domains. However, the role of AKAP12 expression in ulcerative colitis (UC) patients has not been yet described. The aim of the study was to describe the gene and protein of AKAP12 expression in patients with UC and its association regarding the disease severity. We included a total of 40 patients with confirmed diagnosis of UC and 25 controls without endoscopic evidence of colitis or neoplasia. The relative quantification of the gene expression was performed by real-time PCR for AKAP12. Kruskal-Wallis was used to test differences among groups, and Spearman correlation to assess the relationship between AKAP12 gene and clinical outcomes. The extent of disease was evaluated using total colonoscopy, and biopsies were taken from rectum segments. The AKAP12 gene expression was increased in colonic mucosa from patients with active UC when compared with UC remission and control group. The overexpression of AKAP12 in patients with UC was associated with the presence of extensive colitis (p = 0.04, RM = 12, IC = 1.29-186.37). AKAP12/CD16 double positive cells were higher in submucosa (p = 0.04), muscular (p < 0.001), and cells from serosa (p < 0.001) in patients affected by UC in comparison to controls. The overexpression of AKAP12 was associated with the extent of disease. This is the first report about the role of AKAP12 in patients with UC suggesting that this gene and its protein could be involved in the modulation of the disease.

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

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.