Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Dig Dis Sci
2007 Oct 01;5210:2766-74. doi: 10.1007/s10620-006-9531-4.
Show Gene links
Show Anatomy links
Carrageenan reduces bone morphogenetic protein-4 (BMP4) and activates the Wnt/beta-catenin pathway in normal human colonocytes.
Bhattacharyya S
,
Borthakur A
,
Dudeja PK
,
Tobacman JK
.
???displayArticle.abstract???
Carrageenans are highly sulfated polysaccharides that are widely used as food additives in the Western diet, in order to improve the texture of processed foods. Although native and degraded carrageenans induce colonic ulcerations, polyps, and colorectal tumors in animal models, very little is known about the effects of carrageenan on human colonocytes. We evaluated effects of lambda-carrageenan (lambdaCGN) on the normal human colonocyte cell line NCM460, using a concentration of 1 mug/ml, about less than one tenth the average daily exposure to carrageenan in the Western diet. We measured secreted bone morphogenetic protein-4 (BMP4) in spent media and quantified its expression by quantitative RT-PCR. Wnt-related genes were measured by an oligonucleotide array. Cellular beta-catenin was quantified by ELISA. We found a marked decline in secreted BMP4 (P < 0.001) following exposure of NCM460 cells to lambdaCGN for 24 hr. Quantitative RT-PCR for BMP4 transcripts revealed 24% and 45% inhibition of expression on days 2 and 4. cDNA gene expression array of Wnt signaling pathway target genes demonstrated significant changes, including 4.5-fold induction of Wnt 9A and suppression of Dickkopf 3 and RHOU genes. Measurement of beta-catenin by ELISA revealed concomitant accumulation with increases of 67.8%, 61.6%, and 73.9% on days 1, 2, and 4, compared to untreated controls. We conclude that treatment of normal human colonocytes with lambdaCGN activated the Wnt/beta-Catenin cascade and suppressed the expression and secretion of BMP4, inducing significant changes in cellular pathways that are associated with both sporadic and juvenile polyps. CGN may influence development of intestinal polyps in vivo by these mechanisms.
Balemans,
Extracellular regulation of BMP signaling in vertebrates: a cocktail of modulators.
2002, Pubmed,
Xenbase
Balemans,
Extracellular regulation of BMP signaling in vertebrates: a cocktail of modulators.
2002,
Pubmed
,
Xenbase
Belford,
Investigation of the ability of several naturally occurring and synthetic polyanions to bind to and potentiate the biological activity of acidic fibroblast growth factor.
1993,
Pubmed
Benitz,
Intestinal effects of carrageenans in the rhesus monkey (Macaca mulatta).
1973,
Pubmed
Bienz,
Linking colorectal cancer to Wnt signaling.
2000,
Pubmed
Cunha,
The pivotal role of tumour necrosis factor alpha in the development of inflammatory hyperalgesia.
1992,
Pubmed
Daigo,
Novel human, mouse and xenopus genes encoding a member of the RAS superfamily of low-molecular-weight GTP-binding proteins and its downregulation in W/WV mouse jejunum.
2004,
Pubmed
,
Xenbase
Elsayed,
Expression of tissue factor and interleukin-1 beta in a novel rabbit model of disseminated intravascular coagulation induced by carrageenan and lipopolysaccharide.
1995,
Pubmed
Ftouh,
Down-regulation of Dickkopf 3, a regulator of the Wnt signalling pathway, in elderly schizophrenic subjects.
2005,
Pubmed
Hardwick,
Bone morphogenetic protein 2 is expressed by, and acts upon, mature epithelial cells in the colon.
2004,
Pubmed
He,
BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-beta-catenin signaling.
2004,
Pubmed
Hoang,
Dickkopf 3 inhibits invasion and motility of Saos-2 osteosarcoma cells by modulating the Wnt-beta-catenin pathway.
2004,
Pubmed
Hoffman,
Selective inhibition of cell proliferation and DNA synthesis by the polysulphated carbohydrate l-carrageenan.
1995,
Pubmed
Hoffman,
Inhibition of binding of basic fibroblast growth factor to low and high affinity receptors by carrageenans.
1993,
Pubmed
Hoffman,
Carrageenans inhibit growth-factor binding.
1993,
Pubmed
Howe,
Germline mutations of the gene encoding bone morphogenetic protein receptor 1A in juvenile polyposis.
2001,
Pubmed
Ianaro,
Expression of TGF-beta in attenuated Salmonella typhimurium: oral administration leads to the reduction of inflammation, IL-2 and IFN-gamma, but enhancement of IL-10, in carrageenin-induced oedema in mice.
1995,
Pubmed
Ishai-Michaeli,
Heparanase activity expressed by platelets, neutrophils, and lymphoma cells releases active fibroblast growth factor from extracellular matrix.
1990,
Pubmed
Ishiguro,
Syndecan-4 deficiency increases susceptibility to kappa-carrageenan-induced renal damage.
2001,
Pubmed
Kim,
Oncogenic beta-catenin is required for bone morphogenetic protein 4 expression in human cancer cells.
2002,
Pubmed
Kirikoshi,
Expression of WNT14 and WNT14B mRNAs in human cancer, up-regulation of WNT14 by IFNgamma and up-regulation of WNT14B by beta-estradiol.
2001,
Pubmed
Kirikoshi,
Expression of WRCH1 in human cancer and down-regulation of WRCH1 by beta-estradiol in MCF-7 cells.
2002,
Pubmed
Kuhnert,
Essential requirement for Wnt signaling in proliferation of adult small intestine and colon revealed by adenoviral expression of Dickkopf-1.
2004,
Pubmed
Moyer,
NCM460, a normal human colon mucosal epithelial cell line.
1996,
Pubmed
NULL,
Carrageenan.
1983,
Pubmed
Nateri,
Interaction of phosphorylated c-Jun with TCF4 regulates intestinal cancer development.
2005,
Pubmed
Nishanian,
Suppression of tumorigenesis and activation of Wnt signaling by bone morphogenetic protein 4 in human cancer cells.
2004,
Pubmed
Okuda,
Comparison of the activation and interleukin-1 production of mouse peritoneal macrophages by three types of purified carrageenan.
1986,
Pubmed
Piek,
Suppressor and oncogenic roles of transforming growth factor-beta and its signaling pathways in tumorigenesis.
2001,
Pubmed
Pinto,
Canonical Wnt signals are essential for homeostasis of the intestinal epithelium.
2003,
Pubmed
Polakis,
Wnt signaling and cancer.
2000,
Pubmed
Polakis,
The oncogenic activation of beta-catenin.
1999,
Pubmed
Shih,
The beta-catenin binding domain of adenomatous polyposis coli is sufficient for tumor suppression.
2000,
Pubmed
Siegel,
Cytostatic and apoptotic actions of TGF-beta in homeostasis and cancer.
2003,
Pubmed
Tao,
Wrch-1, a novel member of the Rho gene family that is regulated by Wnt-1.
2001,
Pubmed
Tkachenko,
Syndecans: new kids on the signaling block.
2005,
Pubmed
Tobacman,
Review of harmful gastrointestinal effects of carrageenan in animal experiments.
2001,
Pubmed
Utsunomiya,
Differential effects of indomethacin and dexamethasone on cytokine production in carrageenin-induced rat pleurisy.
1994,
Pubmed
Utsunomiya,
Sequential appearance of IL-1 and IL-6 activities in rat carrageenin-induced pleurisy.
1991,
Pubmed
Yu,
Structural studies on kappa-carrageenan derived oligosaccharides.
2002,
Pubmed
Zhou,
Germline mutations in BMPR1A/ALK3 cause a subset of cases of juvenile polyposis syndrome and of Cowden and Bannayan-Riley-Ruvalcaba syndromes.
2001,
Pubmed
Zimmermann,
The syndecans, tuners of transmembrane signaling.
1999,
Pubmed
von Bubnoff,
Intracellular BMP signaling regulation in vertebrates: pathway or network?
2001,
Pubmed
,
Xenbase