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Inflammatory hypoxia induces syndecan-2 expression through IL-1 beta-mediated FOXO3a activation in colonic epithelia

Title
Inflammatory hypoxia induces syndecan-2 expression through IL-1 beta-mediated FOXO3a activation in colonic epithelia
Authors
Choi, SojoongChung, HeesungHong, HeejeongKim, So YeonKim, Seong-EunSeoh, Ju-YoungMoon, Chang MoYang, Eun GyeongOh, Eok-Soo
Ewha Authors
서주영오억수김성은문창모정희성
SCOPUS Author ID
서주영scopus; 오억수scopus; 김성은scopus; 문창모scopus
Issue Date
2017
Journal Title
FASEB JOURNAL
ISSN
0892-6638JCR Link1530-6860JCR Link
Citation
vol. 31, no. 4, pp. 1516 - 1530
Keywords
colon cancerFOXO3aIL-1 beta
Publisher
FEDERATION AMER SOC EXP BIOL
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Chronic inflammation is known to be a key causative factor in tumor progression, but we do not yet fully understand the molecular mechanism through which inflammation leads to cancer. Here, we report that the dextran sulfate sodium (DSS)-induced mouse model of chronic colitis is associated with increases in the serum level of IL-1 beta and the colonic epithelial expression of the cell-surface heparan sulfate proteoglycan, syndecan-2. We further show that IL-1b stimulated the transcription of syndecan-2 via NF-kappa B-dependent FOXO3a activation in CCD841CoN normal colonic epithelial cells and early-stage HT29 colon cancer cells. Inflammatory hypoxia was observed in the colonic epithelia of mice with chronic colitis, suggesting that hypoxic stress is involved in the regulation of syndecan-2 expression. Consistently, experimental inflammatory hypoxia induced hypoxia inducible factor-1 alpha-dependent FOXO3a expression and the p38 MAPK-mediated nuclear localization of FOXO3a. FOXO3a directly mediated syndecan-2 expression in both cell lines and the colonic epithelia of mice with DSS-induced colitis. Moreover, syndecan-2 expression was detected in azoxymethane/ DSS-induced colon tumors. Together, these data demonstrate that inflammatory hypoxia upregulates syndecan-2 via the IL-1 beta-NF-kappa B-FOXO3a pathway. These findings provide new mechanistic insights into inflammatory hypoxia-mediated syndecan-2 expression to connect chronic inflammation and the development of colon cancer.-Choi, S., Chung, H., Hong, H., Kim, S. Y., Kim, S.-E., Seoh, J.-Y., Moon, C. M., Yang, E. G., Oh, E.-S. Inflammatory hypoxia induces syndecan-2 expression through IL-1b-mediated FOXO3a activation in colonic epithelia. FASEB J. 31, 1516-1530 (2017). www.fasebj.org
DOI
10.1096/fj.201601098R
Appears in Collections:
의과대학 > 의학과 > Journal papers
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