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Application of Comparative Transcriptional Genomics to Identify Molecular Targets for Pediatric IBD.

Fang K, Grisham MB, Kevil CG - Front Immunol (2015)

Bottom Line: By comparing the two sets of pediatric IBD microarray data, we found 83 genes were differentially expressed in a similar manner between pediatric Crohn's disease and ulcerative colitis.Up-regulation of the chemokine (C-C motif) ligand 2 (CCL2) gene that maps to 17q12, a confirmed IBD susceptibility loci, indicates that our comparison study can reveal known genetic associations with IBD.In comparing pediatric IBD and experimental colitis microarray data, we found common signatures amongst them including: (1) up-regulation of CXCL9 and S100A8; (2) cytokine-cytokine receptor pathway dysregulation; and (3) over-represented IRF1 and IRF2 transcription binding sites in the promoter region of up-regulated genes, and HNF1A and Lhx3 binding sites were over-represented in the promoter region of the down-regulated genes.

View Article: PubMed Central - PubMed

Affiliation: Division of Digestive Diseases, Inflammatory Bowel Disease Center, David Geffen School of Medicine at UCLA , Los Angeles, CA , USA.

ABSTRACT
Experimental models of colitis in mice have been used extensively for analyzing the molecular events that occur during inflammatory bowel disease (IBD) development. However, it is uncertain to what extent the experimental models reproduce features of human IBD. This is largely due to the lack of precise methods for direct and comprehensive comparison of mouse and human inflamed colon tissue at the molecular level. Here, we use global gene expression patterns of two sets of pediatric IBD and two mouse models of colitis to obtain a direct comparison of the genome signatures of mouse and human IBD. By comparing the two sets of pediatric IBD microarray data, we found 83 genes were differentially expressed in a similar manner between pediatric Crohn's disease and ulcerative colitis. Up-regulation of the chemokine (C-C motif) ligand 2 (CCL2) gene that maps to 17q12, a confirmed IBD susceptibility loci, indicates that our comparison study can reveal known genetic associations with IBD. In comparing pediatric IBD and experimental colitis microarray data, we found common signatures amongst them including: (1) up-regulation of CXCL9 and S100A8; (2) cytokine-cytokine receptor pathway dysregulation; and (3) over-represented IRF1 and IRF2 transcription binding sites in the promoter region of up-regulated genes, and HNF1A and Lhx3 binding sites were over-represented in the promoter region of the down-regulated genes. In summary, this study provides a comprehensive view of transcriptome changes between different pediatric IBD populations in comparison with different colitis models. These findings reveal several new molecular targets for further study in the regulation of colitis.

No MeSH data available.


Related in: MedlinePlus

Network 2 of pediatric UC has biological functions associated with connective tissue disorders, genetic disorder, and dermatological diseases and conditions. Red shading indicates up-regulation, whereas green shading shows down-regulation.
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Figure 5: Network 2 of pediatric UC has biological functions associated with connective tissue disorders, genetic disorder, and dermatological diseases and conditions. Red shading indicates up-regulation, whereas green shading shows down-regulation.

Mentions: Figure 4 shows the first network of pediatric UC with functions related to cellular movement and signaling. Pediatric UC network 1 is mainly composed of eleven G-protein-coupled receptors, which were all up-regulated. Transcription of eight members of the collage family was up-regulated as shown in Figure 5, with functions related to connective tissue. Interestingly, ChI3L1 was in the center of the pediatric UC network 2 (Figure 5), and ChI3L1 indirectly interacts with COL16A2 and TNC.


Application of Comparative Transcriptional Genomics to Identify Molecular Targets for Pediatric IBD.

Fang K, Grisham MB, Kevil CG - Front Immunol (2015)

Network 2 of pediatric UC has biological functions associated with connective tissue disorders, genetic disorder, and dermatological diseases and conditions. Red shading indicates up-regulation, whereas green shading shows down-regulation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4457140&req=5

Figure 5: Network 2 of pediatric UC has biological functions associated with connective tissue disorders, genetic disorder, and dermatological diseases and conditions. Red shading indicates up-regulation, whereas green shading shows down-regulation.
Mentions: Figure 4 shows the first network of pediatric UC with functions related to cellular movement and signaling. Pediatric UC network 1 is mainly composed of eleven G-protein-coupled receptors, which were all up-regulated. Transcription of eight members of the collage family was up-regulated as shown in Figure 5, with functions related to connective tissue. Interestingly, ChI3L1 was in the center of the pediatric UC network 2 (Figure 5), and ChI3L1 indirectly interacts with COL16A2 and TNC.

Bottom Line: By comparing the two sets of pediatric IBD microarray data, we found 83 genes were differentially expressed in a similar manner between pediatric Crohn's disease and ulcerative colitis.Up-regulation of the chemokine (C-C motif) ligand 2 (CCL2) gene that maps to 17q12, a confirmed IBD susceptibility loci, indicates that our comparison study can reveal known genetic associations with IBD.In comparing pediatric IBD and experimental colitis microarray data, we found common signatures amongst them including: (1) up-regulation of CXCL9 and S100A8; (2) cytokine-cytokine receptor pathway dysregulation; and (3) over-represented IRF1 and IRF2 transcription binding sites in the promoter region of up-regulated genes, and HNF1A and Lhx3 binding sites were over-represented in the promoter region of the down-regulated genes.

View Article: PubMed Central - PubMed

Affiliation: Division of Digestive Diseases, Inflammatory Bowel Disease Center, David Geffen School of Medicine at UCLA , Los Angeles, CA , USA.

ABSTRACT
Experimental models of colitis in mice have been used extensively for analyzing the molecular events that occur during inflammatory bowel disease (IBD) development. However, it is uncertain to what extent the experimental models reproduce features of human IBD. This is largely due to the lack of precise methods for direct and comprehensive comparison of mouse and human inflamed colon tissue at the molecular level. Here, we use global gene expression patterns of two sets of pediatric IBD and two mouse models of colitis to obtain a direct comparison of the genome signatures of mouse and human IBD. By comparing the two sets of pediatric IBD microarray data, we found 83 genes were differentially expressed in a similar manner between pediatric Crohn's disease and ulcerative colitis. Up-regulation of the chemokine (C-C motif) ligand 2 (CCL2) gene that maps to 17q12, a confirmed IBD susceptibility loci, indicates that our comparison study can reveal known genetic associations with IBD. In comparing pediatric IBD and experimental colitis microarray data, we found common signatures amongst them including: (1) up-regulation of CXCL9 and S100A8; (2) cytokine-cytokine receptor pathway dysregulation; and (3) over-represented IRF1 and IRF2 transcription binding sites in the promoter region of up-regulated genes, and HNF1A and Lhx3 binding sites were over-represented in the promoter region of the down-regulated genes. In summary, this study provides a comprehensive view of transcriptome changes between different pediatric IBD populations in comparison with different colitis models. These findings reveal several new molecular targets for further study in the regulation of colitis.

No MeSH data available.


Related in: MedlinePlus