Abstract
Background: The α7-subunit of the α7-nicotinic acetylcholine receptor (α7-nAChR) is an obligatory intermediate for the anti-inflammatory effects of the vagus nerve. But in humans, there exists a second gene called CHRFAM7A that encodes a dominant negative α7-nAChR inhibitor. Here, we investigated whether their expression was altered in inflammatory bowel disease (IBD) and colon cancer.Methods: Quantitative RT-PCR measured gene expression of human α7-nAChR gene (CHRNA7), CHRFAM7A, TBC3D1, and actin in biopsies of normal large and small intestine, and compared to their expression in biopsies of ulcerative colitis, Crohn's disease, and colon cancer.Results: qRT-PCR showed that CHRFAM7A and CHRNA7 gene expression was significantly (p<.02) up-regulated in IBD (N=64). Gene expression was unchanged in colon cancer. Further analyses revealed that there were differences in ulcerative colitis and Crohn's Disease. Colon biopsies of ulcerative colitis (N=33) confirmed increased expression of CHRFAM7A and decreased in CHRNA7 expression (p<0.001). Biopsies of Crohn's disease (N=31), however, showed only small changes in CHRFAM7A expression (p<0.04) and no change in CHRNA7. When segregated by tissue source, both CHRFAM7A up-regulation (p<0.02) and CHRNA7 down-regulation (p<0.001) were measured in colon, but not in small intestine.Conclusion: The human-specific CHRFAM7A gene is up-regulated, and its target, CHRNA7, down-regulated, in IBD. Differences between ulcerative colitis and Crohn's disease tie to location of disease.Significance: The appearance of IBD in modern humans may be consequent to the emergence of CHRFAM7A, a human-specific α7-nAChR antagonist. CHRFAM7A could present a new, unrecognized target for development of IBD therapeutics.
Highlights
The emergence of human-specific genes (HSG) in the course of human evolution are presumed to have enabled the adaptation of humans to new environments and new behaviors [1,2,3,4,5,6,7,8,9] but their specific physiological functions are often unknown
It raises the possibility that CHRFAM7A expression in peripheral tissues [20,21] could be associated with human inflammatory disease like, for example, inflammatory bowel disease (IBDs)
The characteristics of the commercially available gene expression arrays of human IBD and colon cancer used in these studies are publicly available http://www.origene.com/qPCR/Tissue-qPCR-Arrays.aspx and include information regarding gender, age, tissue of origin, case diagnosis from donor institutions, histological sections, and pathology verification reports
Summary
The α7-subunit of the α7-nicotinic acetylcholine receptor (α7-nAChR) is an obligatory intermediate for the anti-inflammatory effects of the vagus nerve. We investigated whether their expression was altered in inflammatory bowel disease (IBD) and colon cancer. Methods: Quantitative RT-PCR measured gene expression of human α7-nAChR gene (CHRNA7), CHRFAM7A, TBC3D1, and actin in biopsies of normal large and small intestine, and compared to their expression in biopsies of ulcerative colitis, Crohn's disease, and colon cancer. Results: qRT-PCR showed that CHRFAM7A and CHRNA7 gene expression was significantly (p b .02) up-regulated in IBD (N = 64). Colon biopsies of ulcerative colitis (N = 33) confirmed increased expression of CHRFAM7A and decreased in CHRNA7 expression (p b 0.001). Biopsies of Crohn's disease (N = 31), showed only small changes in CHRFAM7A expression (p b 0.04) and no change in CHRNA7. Conclusion: The human-specific CHRFAM7A gene is up-regulated, and its target, CHRNA7, down-regulated, in IBD. CHRFAM7A could present a new, unrecognized target for development of IBD therapeutics
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