Paclitaxel Interrupts TGF-β1 Signaling Between Gallbladder Epithelial Cells and Myofibroblasts
| Autor: | Jae Woon Choi, Rahul Kuver, Sum P. Lee, Ho Soon Choi, Christopher E. Savard |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Lipopolysaccharides
Cell signaling Pathology medicine.medical_specialty Paclitaxel medicine.medical_treatment Cell Communication Biology Article Collagen Type I Transforming Growth Factor beta1 Mice medicine Animals RNA Messenger Cells Cultured Cell Proliferation L-Lactate Dehydrogenase Tumor Necrosis Factor-alpha Gallbladder Epithelial Cells Fibroblasts Fibrosis Epithelium Mice Inbred C57BL medicine.anatomical_structure Cytokine Biliary tract Cancer research Surgery Tumor necrosis factor alpha Signal transduction Myofibroblast Signal Transduction |
| Zdroj: | Journal of Surgical Research. 141:183-191 |
| ISSN: | 0022-4804 |
| Popis: | The cellular and molecular mechanisms of fibrogenesis in the extrahepatic biliary epithelium are not known. Transforming growth factor-beta1 (TGF-beta1) 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-beta1 signaling between biliary epithelial cells and subepithelial myofibroblasts.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).Exposure to Escherichia coli lipopolysaccharide (LPS) enhanced TGF-beta1 mRNA expression and stimulated TGF-beta1 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-beta1. GBMF also expressed TGF-beta1 mRNA, whose levels were enhanced by exposure to either LPS or exogenous TGF-beta1. PT inhibited LPS-induced TGF-beta1 mRNA expression and protein secretion in GBEC in both culture systems. Tumor necrosis factor-alpha mRNA expression and protein secretion were not affected by PT in GBEC, demonstrating that the effects were specific for TGF-beta1. PT also inhibited LPS- and TGF-beta1-induced collagen I mRNA expression and protein secretion in GBMF.These findings support a model in which GBEC communicate with subepithelial GBMF via TGF-beta1, leading to collagen deposition and fibrosis, and in which GBMF possess autocrine mechanisms involving TGF-beta1 that could regulate collagen production. PT inhibits these fibrogenic pathways. |
| Databáze: | OpenAIRE |
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