DNA Methylation Status of Epithelial-Mesenchymal Transition EMT - Related Genes Is Associated with Severe Clinical Phenotypes in Ulcerative Colitis UCReport as inadecuate




DNA Methylation Status of Epithelial-Mesenchymal Transition EMT - Related Genes Is Associated with Severe Clinical Phenotypes in Ulcerative Colitis UC - Download this document for free, or read online. Document in PDF available to download.

Background

Epithelial-to-mesenchymal transition EMT is a phenomenon that allows the conversion of adherent epithelial cells to a mesenchymal cell phenotype, which enhances migratory capacity and invasiveness. Recent studies have suggested that EMT contributes to the pathogenesis of ulcerative colitis UC. We investigated the promoter DNA methylation status of EMT-related genes in the colonic mucosa in UC.

Methods

Colonic biopsies were obtained from the rectal inflammatory mucosa of 86 UC patients and the non-inflammatory proximal colonic mucosa of 10 paired patients. Bisulfite pyrosequencing was used to quantify the methylation of 5 candidate CpG island promoters NEUROG1, CDX1, miR-1247, CDH1, and CDH13 and LINE1.

Results

Using an unsupervised hierarchical clustering analysis, inflamed rectal mucosa was well separated from mucosa that appeared normal. The CDH1 and CDH13 promoters were significantly associated with patient age p = 0.04, 0.03, respectively. A similar trend was found between those genes and the duration of disease CDH1: p = 0.07, CDH13: p = 0.0002, mean of both: p<0.00001. Several positive associations were found between hypermethylation and severe clinical phenotypes CDX1 and miR-1247 and a refractory phenotype: p = 0.04 and 0.006, respectively. miR-1247 and CDH1 hyper methylation and a more severe Mayo endoscopic subscore: miR-1247: p = 0.0008, CDH1: p = 0.03, mean of both: p = 0.003. When the severe clinical phenotype was defined as having any of five phenotypes hospitalized more than twice, highest Mayo endoscopic subscore, steroid dependence, refractory, or a history of surgery miR-1247 hypermethylation was associated with the same phenotype p = 0.008.

Conclusions

Our data suggest that variability in the methylation status of EMT-related genes is associated with more severe clinical phenotypes in UC.



Author: Tomomitsu Tahara , Tomoyuki Shibata, Masaaki Okubo, Takamitsu Ishizuka, Masakatsu Nakamura, Mitsuo Nagasaka, Yoshihito Nakagawa,

Source: http://plos.srce.hr/



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