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Identification of Novel Therapeutic Molecular Targets in Inflammatory

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Vital and Distinct Roles of H2A.Z Isoforms in Hepatocellular Carcinoma

Sachin Mohan,1– 3 Shaffer Mok,4 Thomas Judge5

1Department of Gastroenterology and Hepatology, University of Minnesota School of Medicine, St Paul, MN, USA; 2Regions Hospital, Department of Gastroenterology and Hepatology, St Paul, MN, USA; 3Health Partners Digestive Care Center, St Paul, MN, 55130, USA; 4Division of Gastroenterology and Hepatology, University Hospital Digestive Health Institute, Westlake, OH 44145, USA; 5Division of Gastroenterology and Liver Diseases, Cooper University Hospital, Mount Laurel, NJ 08054, USA

Correspondence: Sachin Mohan
Regions Hospital, Department of Gastroenterology and Hepatology, 435 Phalen Blvd, St Paul, MN 55130, USA
Tel +1 651-254-8680
Fax +1 651-254-8656
Email sachinmohan01@gmail.com

Purpose: Utilization of genetic databases to identify genes involved in ulcerative colitis (UC), Crohn’s disease (CD), and their extra-intestinal manifestations.
Methods: Protein coding genes involved in ulcerative colitis (3783 genes), Crohn’s disease (3980 genes), uveitis (1043 genes), arthritis (5583 genes), primary sclerosing cholangitis (PSC) (1313 genes), and pyoderma gangrenosum (119 genes) were categorized using four genetic databases. These include Genecards: The Human Gene Database (www.genecards.org), DisGeNET (https://www.disgenet.org/), The Comparative Toxicogenomics Database (http://ctdbase.org/) and the Universal Protein Resource (https://www.uniprot.org/). NDex, Network Data Exchange (http://www.ndexbio.org/), was then utilized for mapping a unique signal pathway from the identified shared genes involved in the above disease processes.
Results: We have detected a unique array of 20 genes with the highest probability of overlay in UC, CD, uveitis, arthritis, pyoderma gangrenosum, and PSC. Figure 1 represents the interactome of these 20 protein coding genes. Of note, unique immune modulators in different disease processes are also noted. Interleukin-25 (IL-25) and monensin-resistant homolog 2 (MON-2) are only noted in UC, CD, pyoderma gangrenosum, and arthritis. Arachidonate 5-lipoxygenase (ALOX5) is involved in UC, CD, and arthritis. SLCO1B3 is exclusively involved with pyoderma gangrenosum, UC, and CD. As expected, TNF involvement is noted in CD, UC, PSC, and arthritis. Table 1 depicts the detailed result.
Conclusion: Our work has identified a distinctive set of genes involved in IBD and its associated extra-intestinal disease processes. These genes play crucial roles in mechanisms of immune response, inflammation, and apoptosis and further our understanding of this complex disease process. We postulate that these genes play a critical role at intersecting pathways involved in inflammatory bowel disease, and these novel molecules, their upstream and downstream effectors, are potential targets for future therapeutic agents.

Keywords: inflammatory bowel diseases, IBD, ulcerative colitis, UC, Crohn’s disease, CD, arthritis, primary sclerosing cholangitis, PSC, uveitis, pyoderma gangrenosum

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