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P765 Transcriptome of intestinal epithelial barrier genes in the colonic mucosa from patients with ulcerative colitis

Fonseca Camarillo G., Iturriaga Goyon E., Yamamoto Furusho J.K.

Instituto Nacional de Ciencias Médicas y Nutriciόn Salvador Zubiran, Inflammatory Bowel Disease Clinic. Department of Gastroenterology, Mexico City, Mexico

Background

Defects in the intestinal epithelial barrier function have been observed in patients with Ulcerative Colitis (UC). It is now becoming evident that an aberrant epithelial barrier function plays a central role in the pathophysiology of UC. Truncated forms of the adherents junction protein E-cadherin (encoded by CDH1) are associated with Crohn's disease. However, genes involved in the epithelial barrier function (ECM1, LAMB1, CDH1, NLRP6, PTGER4 and LRG5) has not been yet described in patients with UC.The aim was to the study the transcriptome panel of genes (ECM1, LAMB1, CDH1, NLRP6, PTGER4 and LRG5) in the colonic mucosa from UC patients.

Methods

We studied a total of 100 patients with definitive diagnosis of UC (50 active and 50 remission) and non-inflamed control group (N=50) without endoscopic evidence of intestinal inflammation. In all groups, the ECM1, LAMB1, CDH1, NLRP6, PTGER4 and LRG5 gene expression were measured by real-time polymerase chain reaction (RT-PCR). Expression of GAPDH a housekeeping gene was analyzed for normalization purposes and quality controls. Statistical analysis was performed using the SPSS 19 program by the Kruskal-Wallis One Way Analysis of Variance on Ranks Data were expressed as the median, range and mean ± SE. A P value ≤0.05 was considered as significant.

Results

LAMB1 gene expression was decreased in remission UC compared to active UC patients and controls (p=0.024 and p=0.03, respectively). CDH1 expression was increased in colonic mucosa from patients with active UC when compared with control group (p=0.043 and p=0.05). Conversely, the ECM1 expression was decreased in patients with active UC compared to UC patients in remission and normal control group (p=0.05 and p=0.003, respectively). The ECM1 levels were decreased in UC remission compared to the normal control group (p=0.017). NLRP6 gene expression was increased in UC patients with histological remission compared with active UC and control group (p=0.013 and p=0.022). PTGER4 expression was increased in patients with UC remission compared to active group and normal control group (p=0.055 and p=0.050). LRG5 gene expression was increased in patients with active UC compared with remission and normal control group (p=0.043 and p=0.028).

Conclusion

This is the first depiction of the description of gene expression of CDH1, LAMB1, ECM1, NLRP6, PTGER4 and LRG5 genes in the colonic mucosa from patients with UC, suggesting that these genes could be involved with defects in the intestinal epithelial barrier in patients with Ulcerative Colitis (UC).