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Role of DDX3 in the pathogenesis of inflammatory bowel disease

When crypt stem cells of the gastrointestinal tract become injured, the result is increased synthesis of pro-inflammatory cytokines and matrix metalloproteinases by their progeny – the colonic epithelium. Chronic inflammation of the gastrointestinal tract is a characteristic of inflammatory bowel di...

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Autores principales: Tantravedi, Saritha, Vesuna, Farhad, Winnard, Paul T., Van Voss, Marise R. Heerma, Van Diest, Paul J., Raman, Venu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777771/
https://www.ncbi.nlm.nih.gov/pubmed/29383159
http://dx.doi.org/10.18632/oncotarget.23323
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author Tantravedi, Saritha
Vesuna, Farhad
Winnard, Paul T.
Van Voss, Marise R. Heerma
Van Diest, Paul J.
Raman, Venu
author_facet Tantravedi, Saritha
Vesuna, Farhad
Winnard, Paul T.
Van Voss, Marise R. Heerma
Van Diest, Paul J.
Raman, Venu
author_sort Tantravedi, Saritha
collection PubMed
description When crypt stem cells of the gastrointestinal tract become injured, the result is increased synthesis of pro-inflammatory cytokines and matrix metalloproteinases by their progeny – the colonic epithelium. Chronic inflammation of the gastrointestinal tract is a characteristic of inflammatory bowel disease, which includes Crohn’s Disease and Ulcerative Colitis. In our ongoing investigation to decipher the characteristic functions of a RNA helicase gene, DDX3, we identified high DDX3 expression by immunohistochemistry of colon biopsy samples, which included chronic/mild Morbus Crohn, active Morbus Crohn, Chronic/mild Colitis Ulcerosa and active Colitis Ulcerosa in epithelium and stromal compartments. We used a small molecule inhibitor of DDX3, RK-33, on two human colonic epithelial cell lines, HCEC1CT and HCEC2CT and found that RK-33 was able to decrease expression of MMP-1, MMP-2, MMP-3, and MMP-10. Moreover, forced differentiation of a human colonic cancer cell line, HT29, resulted in decreased DDX3 levels, indicating that DDX3 contributes to the modulation of colonic epithelium differentiation. In conclusion, our results revealed novel functions of DDX3 in inflammatory bowel disease and indicate a potential for using RK-33 as a systemic therapy to promote not only differentiation of transformed colonic epithelium but also to reduce MMP expression and thus elicit a decreased inflammatory response.
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spelling pubmed-57777712018-01-30 Role of DDX3 in the pathogenesis of inflammatory bowel disease Tantravedi, Saritha Vesuna, Farhad Winnard, Paul T. Van Voss, Marise R. Heerma Van Diest, Paul J. Raman, Venu Oncotarget Research Paper When crypt stem cells of the gastrointestinal tract become injured, the result is increased synthesis of pro-inflammatory cytokines and matrix metalloproteinases by their progeny – the colonic epithelium. Chronic inflammation of the gastrointestinal tract is a characteristic of inflammatory bowel disease, which includes Crohn’s Disease and Ulcerative Colitis. In our ongoing investigation to decipher the characteristic functions of a RNA helicase gene, DDX3, we identified high DDX3 expression by immunohistochemistry of colon biopsy samples, which included chronic/mild Morbus Crohn, active Morbus Crohn, Chronic/mild Colitis Ulcerosa and active Colitis Ulcerosa in epithelium and stromal compartments. We used a small molecule inhibitor of DDX3, RK-33, on two human colonic epithelial cell lines, HCEC1CT and HCEC2CT and found that RK-33 was able to decrease expression of MMP-1, MMP-2, MMP-3, and MMP-10. Moreover, forced differentiation of a human colonic cancer cell line, HT29, resulted in decreased DDX3 levels, indicating that DDX3 contributes to the modulation of colonic epithelium differentiation. In conclusion, our results revealed novel functions of DDX3 in inflammatory bowel disease and indicate a potential for using RK-33 as a systemic therapy to promote not only differentiation of transformed colonic epithelium but also to reduce MMP expression and thus elicit a decreased inflammatory response. Impact Journals LLC 2017-12-15 /pmc/articles/PMC5777771/ /pubmed/29383159 http://dx.doi.org/10.18632/oncotarget.23323 Text en Copyright: © 2017 Tantravedi et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Tantravedi, Saritha
Vesuna, Farhad
Winnard, Paul T.
Van Voss, Marise R. Heerma
Van Diest, Paul J.
Raman, Venu
Role of DDX3 in the pathogenesis of inflammatory bowel disease
title Role of DDX3 in the pathogenesis of inflammatory bowel disease
title_full Role of DDX3 in the pathogenesis of inflammatory bowel disease
title_fullStr Role of DDX3 in the pathogenesis of inflammatory bowel disease
title_full_unstemmed Role of DDX3 in the pathogenesis of inflammatory bowel disease
title_short Role of DDX3 in the pathogenesis of inflammatory bowel disease
title_sort role of ddx3 in the pathogenesis of inflammatory bowel disease
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777771/
https://www.ncbi.nlm.nih.gov/pubmed/29383159
http://dx.doi.org/10.18632/oncotarget.23323
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