| Tocotrienols have potent antifibrogenic effects in human intestinal fibroblasts. | |
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MedLine Citation:
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PMID: 20684017 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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BACKGROUND: Excessive fibroblast expansion and extracellular matrix (ECM) deposition are key events for the development of bowel stenosis in Crohn's disease (CD) patients. Tocotrienols are vitamin E compounds with proven in vitro antifibrogenic effects on rat pancreatic fibroblasts. We aimed at investigating the effects of tocotrienols on human intestinal fibroblast (HIF) proliferation, apoptosis, autophagy, and synthesis of ECM. METHODS: HIF isolated from CD, ulcerative colitis (UC), and normal intestine were treated with tocotrienol-rich fraction (TRF) from palm oil. HIF proliferation was quantified by (3) H-thymidine incorporation, apoptosis was studied by DNA fragmentation, propidium iodide staining, caspase activation, and poly(ADP-ribose) polymerase cleavage, autophagy was analyzed by quantification of LC3 protein and identification of autophagic vesicles by immunofluorescence and production of ECM components was measured by Western blot. RESULTS: TRF significantly reduced HIF proliferation and prevented basic fibroblast growth factor-induced proliferation in CD and UC, but not control HIF. TRF enhanced HIF death by promoting apoptosis and autophagy. HIF apoptosis, but not autophagy, was prevented by the pan-caspase inhibitor zVAD-fmk, whereas both types of cell death were prevented when the mitochondrial permeability transition pore was blocked by cyclosporin A, demonstrating a key role of the mitochondria in these processes. TRF diminished procollagen type I and laminin γ-1 production by HIF. CONCLUSIONS: Tocotrienols exert multiple effects on HIF, reducing cell proliferation, enhancing programmed cell death through apoptosis and autophagy, and decreasing ECM production. Considering their in vitro antifibrogenic properties, tocotrienols could be useful to treat or prevent bowel fibrosis in CD patients. (Inflamm Bowel Dis 2011). |
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Authors:
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Jeroni Luna; Maria Carme Masamunt; Mariana Rickmann; Rut Mora; Carolina España; Salvadora Delgado; Josep Llach; Eva Vaquero; Miquel Sans |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Inflammatory bowel diseases Volume: 17 ISSN: 1536-4844 ISO Abbreviation: Inflamm. Bowel Dis. Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-02-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9508162 Medline TA: Inflamm Bowel Dis Country: United States |
Other Details:
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Languages: eng Pagination: 732-41 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Crohn's & Colitis Foundation of America, Inc. |
Affiliation:
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Department of Gastroenterology. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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