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Transcriptomic Landscape of Treatment-Naive Ulcerative Colitis.


ABSTRACT: Background and Aims:Ulcerative colitis [UC] is a chronic inflammatory disease that effects the gastrointestinal tract and is considered one of the most prominent and common forms of inflammatory bowel disease [IBD]. This study aimed to define and describe the entire transcriptomic landscape in a well-stratified, treatment-naïve UC patient population compared with control patients by using next-generation technology, RNA-Seq. Methods:Mucosal biopsies from treatment-naïve UC patients [n = 14], and healthy controls [n = 16] underwent RNA-Seq. Principal component analysis [PCA], cell deconvolution methods, and diverse statistical methods were applied to obtain and characterise a dataset of significantly differentially expressed genes [DEGs]. Results:Analyses revealed 1480 significantly DEGs in treatment-naïve UC when compared with controls. Cell populations of monocytes, T cells, neutrophils, B cells/ lymphoid cells, and myeloid cells were increased during inflammation, whereas the fraction of epithelial cells were reduced in UC, which is reflected by the DEGs; 79 DEGs were identified as IBD susceptibility genes, and 58 DEGs were expressed in a gender-specific manner. MUC5B, REG3A, DEFA5, and IL33 might be considered as colorectal cancer [CRC] risk factors following UC in males. AQP9 together with CLDN2 may have a role regulating tissue-specific physiological properties in tight junctions in UC. An additional functional role for AQP9 in the synthesis and/or the function of mucus can be implied. Conclusions:This study reveals new potential players in UC pathogenesis in general, and provides evidence for a gender-dependent pathogenesis for UC. These results can be useful for the development of personalised treatment strategies for UC in the future.

SUBMITTER: Taman H 

PROVIDER: S-EPMC6290885 | BioStudies | 2018-01-01

REPOSITORIES: biostudies

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