Abstract:
AIM:To evaluate ATP-binding cassette (ABC) transporters in colonic pathophysiology as they had recently been related to colorectal cancer (CRC) development. METHODS:Literature search was conducted on PubMed using combinations of the following terms: ABC transporters, ATP binding cassette transporter proteins, inflammatory bowel disease, ulcerative, colitis, Crohn's disease, colorectal cancer, colitis, intestinal inflammation, intestinal carcinogenesis, ABCB1/P-glycoprotein (P-gp/CD243/MDR1), ABCC2/multidrug resistance protein 2 (MRP2) and ABCG2/breast cancer resistance protein (BCRP), Abcb1/Mdr1a, abcc2/Mrp2, abcg2/Bcrp, knock-out mice, tight junction, membrane lipid function. RESULTS:Recently, human studies reported that changes in the levels of ABC transporters were early events in the adenoma-carcinoma sequence leading to CRC. A link between ABCB1, high fat diet and gut microbes in relation to colitis was suggested by the animal studies. The finding that colitis was preceded by altered gut bacterial composition suggests that deletion of Abcb1 leads to fundamental changes of host-microbiota interaction. Also, high fat diet increases the frequency and severity of colitis in specific pathogen-free Abcb1 KO mice. The Abcb1 KO mice might thus serve as a model in which diet/environmental factors and microbes may be controlled and investigated in relation to intestinal inflammation. Potential molecular mechanisms include defective transport of inflammatory mediators and/or phospholipid translocation from one side to the other of the cell membrane lipid bilayer by ABC transporters affecting inflammatory response and/or function of tight junctions, phagocytosis and vesicle trafficking. Also, diet and microbes give rise to molecules which are potential substrates for the ABC transporters and which may additionally affect ABC transporter function through nuclear receptors and transcriptional regulation. Another critical role of ABCB1 was suggested by the finding that ABCB1 expression identifies a subpopulation of pro-inflammatory Th17 cells which were resistant to treatment with glucocorticoids. The evidence for the involvement of ABCC2 and ABCG2 in colonic pathophysiology was weak. CONCLUSION:ABCB1, diet, and gut microbes mutually interact in colonic inflammation, a well-known risk factor for CRC. Further insight may be translated into preventive and treatment strategies.
journal_name
World J Gastroenteroljournal_title
World journal of gastroenterologyauthors
Andersen V,Svenningsen K,Knudsen LA,Hansen AK,Holmskov U,Stensballe A,Vogel Udoi
10.3748/wjg.v21.i41.11862subject
Has Abstractpub_date
2015-11-07 00:00:00pages
11862-76issue
41eissn
1007-9327issn
2219-2840journal_volume
21pub_type
杂志文章abstract:AIM:To investigate disease-specific gene expression profiles of peripheral blood mononuclear cells (PBMCs) from Crohn's disease (CD) patients in clinical remission. METHODS:Patients with CD in clinical remission or with very low disease activity according to the Crohn's disease activity index were genotyped regarding ...
journal_title:World journal of gastroenterology
pub_type: 杂志文章
doi:10.3748/wjg.v24.i11.1196
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journal_title:World journal of gastroenterology
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journal_title:World journal of gastroenterology
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doi:10.3748/wjg.v11.i8.1179
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journal_title:World journal of gastroenterology
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pub_type: 历史文章,杂志文章,评审
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pub_type: 杂志文章,评审
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pub_type: 杂志文章
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更新日期:2011-01-28 00:00:00
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journal_title:World journal of gastroenterology
pub_type: 杂志文章
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journal_title:World journal of gastroenterology
pub_type: 杂志文章
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更新日期:2014-06-28 00:00:00
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pub_type: 杂志文章
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更新日期:2003-06-01 00:00:00
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journal_title:World journal of gastroenterology
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更新日期:2015-11-28 00:00:00
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journal_title:World journal of gastroenterology
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journal_title:World journal of gastroenterology
pub_type: 杂志文章
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更新日期:2008-02-07 00:00:00
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journal_title:World journal of gastroenterology
pub_type: 杂志文章,多中心研究
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更新日期:2014-09-14 00:00:00
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更新日期:2006-10-07 00:00:00