ArticleJournal of pediatric gastroenterology and nutrition2011
Critical role for P-glycoprotein expression in hematopoietic cells in the FVB.Mdr1a(-/-) model of colitis.
Article in Journal of pediatric gastroenterology and nutrition, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 10 citations in OpenAlex.
- P-glycoprotein multidrug transporter in inflammatory bowel diseases: More questions than answers.World journal of gastroenterology · 2017Article
- Novel understanding of ABC transporters ABCB1/MDR/P-glycoprotein, ABCC2/MRP2, and ABCG2/BCRP in colorectal pathophysiology.World journal of gastroenterology · 2015Article
- TLR signaling modulates side effects of anticancer therapy in the small intestine.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- High ABCC2 and low ABCG2 gene expression are early events in the colorectal adenoma-carcinoma sequence.PloS one · 2015Article
- Altered generation of induced regulatory T cells in the FVB.mdr1a-/- mouse model of colitis.Mucosal immunology · 2013Article
- Maintenance of host leukocytes in peripheral immune compartments following lethal irradiation and bone marrow reconstitution: implications for graft versus host disease.Transplant immunology · 2013Article
- Animal models of ulcerative colitis and their application in drug research.Drug design, development and therapy · 2013Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
objectiveP-glycoprotein (P-gp), the functional product of the multidrug resistance gene (MDR), is a transmembrane protein that extrudes substrates from the intracellular environment. P-gp is expressed on the apical surface of epithelial cells and on cells from the hematopoietic lineage. Human MDR polymorphisms have been associated with the increased risk of inflammatory bowel disease, and FVB/N animals deficient in mdr1a expression develop spontaneous colitis. Previous studies using adult bone marrow chimeras indicated that colitis development in this animal model was contingent on P-gp deficiency in radiation-resistant epithelial cells; however, the use of adult animals may mask the role of hematopoietic immune cells in colitis initiation, due to preexisting epithelial abnormalities. SUBJECTS AND
methodsTo assess the importance of P-gp expression in intestinal epithelial and hematopoietic-derived cells on colitis induction in FVB.mdr1a(-/-) animals, we developed a neonatal model of bone marrow reconstitution. FVB/N and FVB.mdr1a(-/-) adult and neonatal animals were lethally irradiated and reconstituted with bone marrow from FVB/N or FVB.mdr1a(-/-) donors. Animals were observed for 20 weeks.
resultsAdult FVB/N animals deficient in P-gp expression in hematopoietically derived immune cells developed colitis similar to adult animals deficient in P-gp expression in radiation-resistant epithelial/stromal cells. Neonatal animals deficient in P-gp expression in hematopoietically derived immune cells developed a more histologically significant colitis than those deficient in P-gp expression in epithelial tissue.
conclusionsThe use of a neonatal model of bone marrow reconstitution has revealed a critical role for P-gp expression in hematopoietically derived immune cells in colitis development in the FVB.mdr1a(-/-) model.
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