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Article: Paclitaxel Interrupts TGF-β1 Signaling Between Gallbladder Epithelial Cells and Myofibroblasts

TitlePaclitaxel Interrupts TGF-β1 Signaling Between Gallbladder Epithelial Cells and Myofibroblasts
Authors
Keywordsbiliary epithelium
cholangitis
fibrosis
gallstones
Issue Date2007
PublisherElsevier Inc.. The Journal's web site is located at http://www.elsevier.com/locate/jsre
Citation
Journal Of Surgical Research, 2007, v. 141 n. 2, p. 183-191 How to Cite?
AbstractBackground: The cellular and molecular mechanisms of fibrogenesis in the extrahepatic biliary epithelium are not known. Transforming growth factor-β1 (TGF-β1) is a cytokine implicated in signaling pathways that mediate collagen formation. An observation that paclitaxel (PT), applied topically into the rat common bile duct, inhibited stricture formation led us to hypothesize that PT's effects might be due to interruption of TGF-β1 signaling between biliary epithelial cells and subepithelial myofibroblasts. Materials and methods: We tested this hypothesis using an in vitro cell-culture model in which murine gallbladder epithelial cells (GBEC) are cultured separately or cocultured with human gallbladder myofibroblasts (GBMF). Results: Exposure to Escherichia coli lipopolysaccharide (LPS) enhanced TGF-β1 mRNA expression and stimulated TGF-β1 protein secretion into both apical and basolateral compartments in GBEC. This effect was more prominent with basolateral secretion and was also more pronounced in the coculture system. In GBMF, collagen I mRNA expression and protein secretion were stimulated by treatment with LPS or TGF-β1. GBMF also expressed TGF-β1 mRNA, whose levels were enhanced by exposure to either LPS or exogenous TGF-β1. PT inhibited LPS-induced TGF-β1 mRNA expression and protein secretion in GBEC in both culture systems. Tumor necrosis factor-α mRNA expression and protein secretion were not affected by PT in GBEC, demonstrating that the effects were specific for TGF-β1. PT also inhibited LPS- and TGF-β1-induced collagen I mRNA expression and protein secretion in GBMF. Conclusions: These findings support a model in which GBEC communicate with subepithelial GBMF via TGF-β1, leading to collagen deposition and fibrosis, and in which GBMF possess autocrine mechanisms involving TGF-β1 that could regulate collagen production. PT inhibits these fibrogenic pathways. © 2007 Elsevier Inc. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/92473
ISSN
2015 Impact Factor: 2.198
2015 SCImago Journal Rankings: 0.928
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChoi, HSen_HK
dc.contributor.authorSavard, CEen_HK
dc.contributor.authorChoi, JWen_HK
dc.contributor.authorKuver, Ren_HK
dc.contributor.authorLee, SPen_HK
dc.date.accessioned2010-09-17T10:47:19Z-
dc.date.available2010-09-17T10:47:19Z-
dc.date.issued2007en_HK
dc.identifier.citationJournal Of Surgical Research, 2007, v. 141 n. 2, p. 183-191en_HK
dc.identifier.issn0022-4804en_HK
dc.identifier.urihttp://hdl.handle.net/10722/92473-
dc.description.abstractBackground: The cellular and molecular mechanisms of fibrogenesis in the extrahepatic biliary epithelium are not known. Transforming growth factor-β1 (TGF-β1) is a cytokine implicated in signaling pathways that mediate collagen formation. An observation that paclitaxel (PT), applied topically into the rat common bile duct, inhibited stricture formation led us to hypothesize that PT's effects might be due to interruption of TGF-β1 signaling between biliary epithelial cells and subepithelial myofibroblasts. Materials and methods: We tested this hypothesis using an in vitro cell-culture model in which murine gallbladder epithelial cells (GBEC) are cultured separately or cocultured with human gallbladder myofibroblasts (GBMF). Results: Exposure to Escherichia coli lipopolysaccharide (LPS) enhanced TGF-β1 mRNA expression and stimulated TGF-β1 protein secretion into both apical and basolateral compartments in GBEC. This effect was more prominent with basolateral secretion and was also more pronounced in the coculture system. In GBMF, collagen I mRNA expression and protein secretion were stimulated by treatment with LPS or TGF-β1. GBMF also expressed TGF-β1 mRNA, whose levels were enhanced by exposure to either LPS or exogenous TGF-β1. PT inhibited LPS-induced TGF-β1 mRNA expression and protein secretion in GBEC in both culture systems. Tumor necrosis factor-α mRNA expression and protein secretion were not affected by PT in GBEC, demonstrating that the effects were specific for TGF-β1. PT also inhibited LPS- and TGF-β1-induced collagen I mRNA expression and protein secretion in GBMF. Conclusions: These findings support a model in which GBEC communicate with subepithelial GBMF via TGF-β1, leading to collagen deposition and fibrosis, and in which GBMF possess autocrine mechanisms involving TGF-β1 that could regulate collagen production. PT inhibits these fibrogenic pathways. © 2007 Elsevier Inc. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherElsevier Inc.. The Journal's web site is located at http://www.elsevier.com/locate/jsreen_HK
dc.relation.ispartofJournal of Surgical Researchen_HK
dc.subjectbiliary epitheliumen_HK
dc.subjectcholangitisen_HK
dc.subjectfibrosisen_HK
dc.subjectgallstonesen_HK
dc.titlePaclitaxel Interrupts TGF-β1 Signaling Between Gallbladder Epithelial Cells and Myofibroblastsen_HK
dc.typeArticleen_HK
dc.identifier.emailLee, SP: sumlee@hku.hken_HK
dc.identifier.authorityLee, SP=rp01351en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.jss.2006.12.558en_HK
dc.identifier.pmid17574589-
dc.identifier.scopuseid_2-s2.0-34447256779en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-34447256779&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume141en_HK
dc.identifier.issue2en_HK
dc.identifier.spage183en_HK
dc.identifier.epage191en_HK
dc.identifier.eissn1095-8673-
dc.identifier.isiWOS:000248284300009-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridChoi, HS=7404339634en_HK
dc.identifier.scopusauthoridSavard, CE=6701738621en_HK
dc.identifier.scopusauthoridChoi, JW=24477421700en_HK
dc.identifier.scopusauthoridKuver, R=6701723533en_HK
dc.identifier.scopusauthoridLee, SP=7601417497en_HK

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