The Experts below are selected from a list of 1476 Experts worldwide ranked by ideXlab platform
Tetsuya Terasaki - One of the best experts on this subject based on the ideXlab platform.
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altered expression of basement membrane related molecules in rat Brain Pericyte endothelial and astrocyte cell lines after transforming growth factor β1 treatment
Drug Metabolism and Pharmacokinetics, 2007Co-Authors: Noriko Kose, Tetsuya Terasaki, Tomoko Asashima, Hisashi Iizasa, Mariko Muta, Yoshimichi Sai, Emi NakashimaAbstract:The basement membrane at the blood-Brain barrier (BBB) plays important roles in maintaining the structure and function of capillary vessels. The BBB is constructed from endothelial cells, astrocytes and Pericytes, but their interactions in the formation or maintenance of basement membrane have not been established. Transforming growth factor-beta1 (TGF-beta1) is known to increase fibronectin in Brain capillary basement membrane with deposition of beta-amyloid. We previously reported that the mRNA level of alpha-smooth muscle actin in a Brain capillary Pericyte cell line TR-PCT1 was increased by treatment with TGF-beta1. In this study, expression of mRNAs encoding basement membrane-related molecules in TR-PCT1, a rat endothelial cell line TR-BBB13, and a type 2 astrocyte cell line TR-AST4 was evaluated by RT-PCR. The effects of TGF-beta1 on expression of basement membrane-related genes in these cell lines were also examined. Fibronectin, MMP-9, tPA, TIMP-1, and PAI-l in TR-PCT1 were higher than in TR-BBB13 and TR-AST4. In TR-PCT1 treated with TGF-beta1, collagen type IV, PAI-1, and MMP-9 were increased, and TIMP-2 was reduced. The change in PAI-1 mRNA was faster than those in MMP-9, TIMP-2, collagen type IV mRNAs. These results suggest that Pericytes may be key cells in the maintenance of the basement membrane at the BBB.
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a Pericyte derived angiopoietin 1 multimeric complex induces occludin gene expression in Brain capillary endothelial cells through tie 2 activation in vitro
Journal of Neurochemistry, 2004Co-Authors: Satoko Hori, Sumio Ohtsuki, Kenichi Hosoya, Emi Nakashima, Tetsuya TerasakiAbstract:Although tight-junctions (TJs) at the blood-Brain barrier (BBB) are important to prevent non-specific entry of compounds into the CNS, molecular mechanisms regulating TJ maintenance remain still unclear. The purpose of this study was therefore to identify molecules, which regulate occludin expression, derived from astrocytes and Pericytes that ensheathe Brain microvessels by using conditionally immortalized adult rat Brain capillary endothelial (TR-BBB13), type II astrocyte (TR-AST4) and Brain Pericyte (TR-PCT1) cell lines. Transfilter co-culture with TR-AST4 cells, and exposure to conditioned medium of TR-AST4 cells (AST-CM) or TR-PCT1 cells (PCT-CM) increased occludin mRNA in TR-BBB13 cells. PCT-CM-induced occludin up-regulation was significantly inhibited by an angiopoietin-1-neutralizing antibody, whereas the up-regulation by AST-CM was not. Immunoprecipitation and western blot analyses confirmed that multimeric angiopoietin-1 is secreted from TR-PCT1 cells, and induces occludin mRNA, acting through tyrosine phosphorylation of Tie-2 in TR-BBB13 cells. A fractionated AST-CM study revealed that factors in the molecular weight range of 30-100 kDa led to occludin induction. Conversely, occludin mRNA was reduced by transforming growth factor beta 1, the mRNA of which was up-regulated in TR-AST4 cells following hypoxic treatment. In conclusion, in vitro BBB model studies revealed that the Pericyte-derived multimeric angiopoietin-1/Tie-2 pathway induces occludin expression.
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a Pericyte derived angiopoietin 1 multimeric complex induces occludin gene expression in Brain capillary endothelial cells through tie 2 activation in vitro
Journal of Neurochemistry, 2004Co-Authors: Satoko Hori, Sumio Ohtsuki, Kenichi Hosoya, Emi Nakashima, Tetsuya TerasakiAbstract:Although tight-junctions (TJs) at the blood–Brain barrier (BBB) are important to prevent non-specific entry of compounds into the CNS, molecular mechanisms regulating TJ maintenance remain still unclear. The purpose of this study was therefore to identify molecules, which regulate occludin expression, derived from astrocytes and Pericytes that ensheathe Brain microvessels by using conditionally immortalized adult rat Brain capillary endothelial (TR-BBB13), type II astrocyte (TR-AST4) and Brain Pericyte (TR-PCT1) cell lines. Transfilter co-culture with TR-AST4 cells, and exposure to conditioned medium of TR-AST4 cells (AST-CM) or TR-PCT1 cells (PCT-CM) increased occludin mRNA in TR-BBB13 cells. PCT-CM-induced occludin up-regulation was significantly inhibited by an angiopoietin-1-neutralizing antibody, whereas the up-regulation by AST-CM was not. Immunoprecipitation and western blot analyses confirmed that multimeric angiopoietin-1 is secreted from TR-PCT1 cells, and induces occludin mRNA, acting through tyrosine phosphorylation of Tie-2 in TR-BBB13 cells. A fractionated AST-CM study revealed that factors in the molecular weight range of 30–100 kDa led to occludin induction. Conversely, occludin mRNA was reduced by transforming growth factor β1, the mRNA of which was up-regulated in TR-AST4 cells following hypoxic treatment. In conclusion, in vitro BBB model studies revealed that the Pericyte-derived multimeric angiopoietin-1/Tie-2 pathway induces occludin expression.
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rat Brain Pericyte cell lines expressing β2 adrenergic receptor angiotensin ii receptor type 1a klotho and cxcr4 mrnas despite having endothelial cell markers
Journal of Cellular Physiology, 2003Co-Authors: Tomoko Asashima, Tetsuya Terasaki, Hisashi Iizasa, Emi NakashimaAbstract:Pericytes are an integral component of blood capillaries, but their involvement in a variety of conditions and diseases, including hypertension and multiple sclerosis, is poorly understood. In order to analyze the mRNA expression of markers related to hypertension and multiple sclerosis in rat Brain Pericytes, we have established Brain capillary Pericyte cell lines from temperature-sensitive SV40 large T antigen transgenic rats. The newly established clones showed similar biochemical and morphological properties to primary Pericytes. The expression of endothelial cell-related markers Flt-1, Flk-1, Tie-1, and Tie-2 was evaluated by RT-PCR analysis. β2-Adrenergic receptor (β2-AR), angiotensin II receptor type1A (AT1A), and klotho were also evaluated as markers related to hypertension and multiple sclerosis. All of the isolated clones expressed β2-AR, AT1A and klotho genes. They also stably expressed Flt-1 and Tie-2, while Flk-1, Tie-1 and CXCR4 were expressed only at low levels in some of the clones. The expressions of AT1 in TR-PCT1 were determined by Western blotting. Angiotensin II stimulated migration of Pericytes. This effect was blocked by an AT1 antagonist. The Pericyte cell lines established here are pluripotent, and should be useful for analysis of the reactivity and biological roles of Pericytes. J. Cell. Physiol. 197: 69–76, 2003© 2003 Wiley-Liss, Inc.
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rat Brain Pericyte cell lines expressing β2 adrenergic receptor angiotensin ii receptor type 1a klotho and cxcr4 mrnas despite having endothelial cell markers
Journal of Cellular Physiology, 2003Co-Authors: Tomoko Asashima, Tetsuya Terasaki, Hisashi Iizasa, Emi NakashimaAbstract:Pericytes are an integral component of blood capillaries, but their involvement in a variety of conditions and diseases, including hypertension and multiple sclerosis, is poorly understood. In order to analyze the mRNA expression of markers related to hypertension and multiple sclerosis in rat Brain Pericytes, we have established Brain capillary Pericyte cell lines from temperature-sensitive SV40 large T antigen transgenic rats. The newly established clones showed similar biochemical and morphological properties to primary Pericytes. The expression of endothelial cell-related markers Flt-1, Flk-1, Tie-1, and Tie-2 was evaluated by RT-PCR analysis. beta2-Adrenergic receptor (beta2-AR), angiotensin II receptor type1A (AT1A), and klotho were also evaluated as markers related to hypertension and multiple sclerosis. All of the isolated clones expressed beta2-AR, AT1A and klotho genes. They also stably expressed Flt-1 and Tie-2, while Flk-1, Tie-1 and CXCR4 were expressed only at low levels in some of the clones. The expressions of AT1 in TR-PCT1 were determined by Western blotting. Angiotensin II stimulated migration of Pericytes. This effect was blocked by an AT1 antagonist. The Pericyte cell lines established here are pluripotent, and should be useful for analysis of the reactivity and biological roles of Pericytes.
Emi Nakashima - One of the best experts on this subject based on the ideXlab platform.
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altered expression of basement membrane related molecules in rat Brain Pericyte endothelial and astrocyte cell lines after transforming growth factor β1 treatment
Drug Metabolism and Pharmacokinetics, 2007Co-Authors: Noriko Kose, Tetsuya Terasaki, Tomoko Asashima, Hisashi Iizasa, Mariko Muta, Yoshimichi Sai, Emi NakashimaAbstract:The basement membrane at the blood-Brain barrier (BBB) plays important roles in maintaining the structure and function of capillary vessels. The BBB is constructed from endothelial cells, astrocytes and Pericytes, but their interactions in the formation or maintenance of basement membrane have not been established. Transforming growth factor-beta1 (TGF-beta1) is known to increase fibronectin in Brain capillary basement membrane with deposition of beta-amyloid. We previously reported that the mRNA level of alpha-smooth muscle actin in a Brain capillary Pericyte cell line TR-PCT1 was increased by treatment with TGF-beta1. In this study, expression of mRNAs encoding basement membrane-related molecules in TR-PCT1, a rat endothelial cell line TR-BBB13, and a type 2 astrocyte cell line TR-AST4 was evaluated by RT-PCR. The effects of TGF-beta1 on expression of basement membrane-related genes in these cell lines were also examined. Fibronectin, MMP-9, tPA, TIMP-1, and PAI-l in TR-PCT1 were higher than in TR-BBB13 and TR-AST4. In TR-PCT1 treated with TGF-beta1, collagen type IV, PAI-1, and MMP-9 were increased, and TIMP-2 was reduced. The change in PAI-1 mRNA was faster than those in MMP-9, TIMP-2, collagen type IV mRNAs. These results suggest that Pericytes may be key cells in the maintenance of the basement membrane at the BBB.
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a Pericyte derived angiopoietin 1 multimeric complex induces occludin gene expression in Brain capillary endothelial cells through tie 2 activation in vitro
Journal of Neurochemistry, 2004Co-Authors: Satoko Hori, Sumio Ohtsuki, Kenichi Hosoya, Emi Nakashima, Tetsuya TerasakiAbstract:Although tight-junctions (TJs) at the blood-Brain barrier (BBB) are important to prevent non-specific entry of compounds into the CNS, molecular mechanisms regulating TJ maintenance remain still unclear. The purpose of this study was therefore to identify molecules, which regulate occludin expression, derived from astrocytes and Pericytes that ensheathe Brain microvessels by using conditionally immortalized adult rat Brain capillary endothelial (TR-BBB13), type II astrocyte (TR-AST4) and Brain Pericyte (TR-PCT1) cell lines. Transfilter co-culture with TR-AST4 cells, and exposure to conditioned medium of TR-AST4 cells (AST-CM) or TR-PCT1 cells (PCT-CM) increased occludin mRNA in TR-BBB13 cells. PCT-CM-induced occludin up-regulation was significantly inhibited by an angiopoietin-1-neutralizing antibody, whereas the up-regulation by AST-CM was not. Immunoprecipitation and western blot analyses confirmed that multimeric angiopoietin-1 is secreted from TR-PCT1 cells, and induces occludin mRNA, acting through tyrosine phosphorylation of Tie-2 in TR-BBB13 cells. A fractionated AST-CM study revealed that factors in the molecular weight range of 30-100 kDa led to occludin induction. Conversely, occludin mRNA was reduced by transforming growth factor beta 1, the mRNA of which was up-regulated in TR-AST4 cells following hypoxic treatment. In conclusion, in vitro BBB model studies revealed that the Pericyte-derived multimeric angiopoietin-1/Tie-2 pathway induces occludin expression.
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a Pericyte derived angiopoietin 1 multimeric complex induces occludin gene expression in Brain capillary endothelial cells through tie 2 activation in vitro
Journal of Neurochemistry, 2004Co-Authors: Satoko Hori, Sumio Ohtsuki, Kenichi Hosoya, Emi Nakashima, Tetsuya TerasakiAbstract:Although tight-junctions (TJs) at the blood–Brain barrier (BBB) are important to prevent non-specific entry of compounds into the CNS, molecular mechanisms regulating TJ maintenance remain still unclear. The purpose of this study was therefore to identify molecules, which regulate occludin expression, derived from astrocytes and Pericytes that ensheathe Brain microvessels by using conditionally immortalized adult rat Brain capillary endothelial (TR-BBB13), type II astrocyte (TR-AST4) and Brain Pericyte (TR-PCT1) cell lines. Transfilter co-culture with TR-AST4 cells, and exposure to conditioned medium of TR-AST4 cells (AST-CM) or TR-PCT1 cells (PCT-CM) increased occludin mRNA in TR-BBB13 cells. PCT-CM-induced occludin up-regulation was significantly inhibited by an angiopoietin-1-neutralizing antibody, whereas the up-regulation by AST-CM was not. Immunoprecipitation and western blot analyses confirmed that multimeric angiopoietin-1 is secreted from TR-PCT1 cells, and induces occludin mRNA, acting through tyrosine phosphorylation of Tie-2 in TR-BBB13 cells. A fractionated AST-CM study revealed that factors in the molecular weight range of 30–100 kDa led to occludin induction. Conversely, occludin mRNA was reduced by transforming growth factor β1, the mRNA of which was up-regulated in TR-AST4 cells following hypoxic treatment. In conclusion, in vitro BBB model studies revealed that the Pericyte-derived multimeric angiopoietin-1/Tie-2 pathway induces occludin expression.
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rat Brain Pericyte cell lines expressing β2 adrenergic receptor angiotensin ii receptor type 1a klotho and cxcr4 mrnas despite having endothelial cell markers
Journal of Cellular Physiology, 2003Co-Authors: Tomoko Asashima, Tetsuya Terasaki, Hisashi Iizasa, Emi NakashimaAbstract:Pericytes are an integral component of blood capillaries, but their involvement in a variety of conditions and diseases, including hypertension and multiple sclerosis, is poorly understood. In order to analyze the mRNA expression of markers related to hypertension and multiple sclerosis in rat Brain Pericytes, we have established Brain capillary Pericyte cell lines from temperature-sensitive SV40 large T antigen transgenic rats. The newly established clones showed similar biochemical and morphological properties to primary Pericytes. The expression of endothelial cell-related markers Flt-1, Flk-1, Tie-1, and Tie-2 was evaluated by RT-PCR analysis. β2-Adrenergic receptor (β2-AR), angiotensin II receptor type1A (AT1A), and klotho were also evaluated as markers related to hypertension and multiple sclerosis. All of the isolated clones expressed β2-AR, AT1A and klotho genes. They also stably expressed Flt-1 and Tie-2, while Flk-1, Tie-1 and CXCR4 were expressed only at low levels in some of the clones. The expressions of AT1 in TR-PCT1 were determined by Western blotting. Angiotensin II stimulated migration of Pericytes. This effect was blocked by an AT1 antagonist. The Pericyte cell lines established here are pluripotent, and should be useful for analysis of the reactivity and biological roles of Pericytes. J. Cell. Physiol. 197: 69–76, 2003© 2003 Wiley-Liss, Inc.
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rat Brain Pericyte cell lines expressing β2 adrenergic receptor angiotensin ii receptor type 1a klotho and cxcr4 mrnas despite having endothelial cell markers
Journal of Cellular Physiology, 2003Co-Authors: Tomoko Asashima, Tetsuya Terasaki, Hisashi Iizasa, Emi NakashimaAbstract:Pericytes are an integral component of blood capillaries, but their involvement in a variety of conditions and diseases, including hypertension and multiple sclerosis, is poorly understood. In order to analyze the mRNA expression of markers related to hypertension and multiple sclerosis in rat Brain Pericytes, we have established Brain capillary Pericyte cell lines from temperature-sensitive SV40 large T antigen transgenic rats. The newly established clones showed similar biochemical and morphological properties to primary Pericytes. The expression of endothelial cell-related markers Flt-1, Flk-1, Tie-1, and Tie-2 was evaluated by RT-PCR analysis. beta2-Adrenergic receptor (beta2-AR), angiotensin II receptor type1A (AT1A), and klotho were also evaluated as markers related to hypertension and multiple sclerosis. All of the isolated clones expressed beta2-AR, AT1A and klotho genes. They also stably expressed Flt-1 and Tie-2, while Flk-1, Tie-1 and CXCR4 were expressed only at low levels in some of the clones. The expressions of AT1 in TR-PCT1 were determined by Western blotting. Angiotensin II stimulated migration of Pericytes. This effect was blocked by an AT1 antagonist. The Pericyte cell lines established here are pluripotent, and should be useful for analysis of the reactivity and biological roles of Pericytes.
Tomoko Asashima - One of the best experts on this subject based on the ideXlab platform.
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altered expression of basement membrane related molecules in rat Brain Pericyte endothelial and astrocyte cell lines after transforming growth factor β1 treatment
Drug Metabolism and Pharmacokinetics, 2007Co-Authors: Noriko Kose, Tetsuya Terasaki, Tomoko Asashima, Hisashi Iizasa, Mariko Muta, Yoshimichi Sai, Emi NakashimaAbstract:The basement membrane at the blood-Brain barrier (BBB) plays important roles in maintaining the structure and function of capillary vessels. The BBB is constructed from endothelial cells, astrocytes and Pericytes, but their interactions in the formation or maintenance of basement membrane have not been established. Transforming growth factor-beta1 (TGF-beta1) is known to increase fibronectin in Brain capillary basement membrane with deposition of beta-amyloid. We previously reported that the mRNA level of alpha-smooth muscle actin in a Brain capillary Pericyte cell line TR-PCT1 was increased by treatment with TGF-beta1. In this study, expression of mRNAs encoding basement membrane-related molecules in TR-PCT1, a rat endothelial cell line TR-BBB13, and a type 2 astrocyte cell line TR-AST4 was evaluated by RT-PCR. The effects of TGF-beta1 on expression of basement membrane-related genes in these cell lines were also examined. Fibronectin, MMP-9, tPA, TIMP-1, and PAI-l in TR-PCT1 were higher than in TR-BBB13 and TR-AST4. In TR-PCT1 treated with TGF-beta1, collagen type IV, PAI-1, and MMP-9 were increased, and TIMP-2 was reduced. The change in PAI-1 mRNA was faster than those in MMP-9, TIMP-2, collagen type IV mRNAs. These results suggest that Pericytes may be key cells in the maintenance of the basement membrane at the BBB.
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rat Brain Pericyte cell lines expressing β2 adrenergic receptor angiotensin ii receptor type 1a klotho and cxcr4 mrnas despite having endothelial cell markers
Journal of Cellular Physiology, 2003Co-Authors: Tomoko Asashima, Tetsuya Terasaki, Hisashi Iizasa, Emi NakashimaAbstract:Pericytes are an integral component of blood capillaries, but their involvement in a variety of conditions and diseases, including hypertension and multiple sclerosis, is poorly understood. In order to analyze the mRNA expression of markers related to hypertension and multiple sclerosis in rat Brain Pericytes, we have established Brain capillary Pericyte cell lines from temperature-sensitive SV40 large T antigen transgenic rats. The newly established clones showed similar biochemical and morphological properties to primary Pericytes. The expression of endothelial cell-related markers Flt-1, Flk-1, Tie-1, and Tie-2 was evaluated by RT-PCR analysis. β2-Adrenergic receptor (β2-AR), angiotensin II receptor type1A (AT1A), and klotho were also evaluated as markers related to hypertension and multiple sclerosis. All of the isolated clones expressed β2-AR, AT1A and klotho genes. They also stably expressed Flt-1 and Tie-2, while Flk-1, Tie-1 and CXCR4 were expressed only at low levels in some of the clones. The expressions of AT1 in TR-PCT1 were determined by Western blotting. Angiotensin II stimulated migration of Pericytes. This effect was blocked by an AT1 antagonist. The Pericyte cell lines established here are pluripotent, and should be useful for analysis of the reactivity and biological roles of Pericytes. J. Cell. Physiol. 197: 69–76, 2003© 2003 Wiley-Liss, Inc.
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rat Brain Pericyte cell lines expressing β2 adrenergic receptor angiotensin ii receptor type 1a klotho and cxcr4 mrnas despite having endothelial cell markers
Journal of Cellular Physiology, 2003Co-Authors: Tomoko Asashima, Tetsuya Terasaki, Hisashi Iizasa, Emi NakashimaAbstract:Pericytes are an integral component of blood capillaries, but their involvement in a variety of conditions and diseases, including hypertension and multiple sclerosis, is poorly understood. In order to analyze the mRNA expression of markers related to hypertension and multiple sclerosis in rat Brain Pericytes, we have established Brain capillary Pericyte cell lines from temperature-sensitive SV40 large T antigen transgenic rats. The newly established clones showed similar biochemical and morphological properties to primary Pericytes. The expression of endothelial cell-related markers Flt-1, Flk-1, Tie-1, and Tie-2 was evaluated by RT-PCR analysis. beta2-Adrenergic receptor (beta2-AR), angiotensin II receptor type1A (AT1A), and klotho were also evaluated as markers related to hypertension and multiple sclerosis. All of the isolated clones expressed beta2-AR, AT1A and klotho genes. They also stably expressed Flt-1 and Tie-2, while Flk-1, Tie-1 and CXCR4 were expressed only at low levels in some of the clones. The expressions of AT1 in TR-PCT1 were determined by Western blotting. Angiotensin II stimulated migration of Pericytes. This effect was blocked by an AT1 antagonist. The Pericyte cell lines established here are pluripotent, and should be useful for analysis of the reactivity and biological roles of Pericytes.
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newly developed rat Brain Pericyte cell line tr pct1 responds to transforming growth factor β1 and β glycerophosphate
European Journal of Cell Biology, 2002Co-Authors: Tomoko Asashima, Kenichi Hosoya, Tetsuya Terasaki, Hisashi Iizasa, Kazuhiro Tetsuka, Masatsugu Ueda, Masuo Obinata, Emi NakashimaAbstract:Brain Pericytes form an incomplete envelope around endothelial cells and within the microvascular basement membrane of capillaries and postcapillary venules. Recently, it has been reported that Brain Pericytes exhibit pluripotency, regulation of endothelial cell activity, and macrophage activity. However, many molecular and cellular aspects of Brain Pericytes remain unclear. In this study, we have tried to establish a conditionally immortalized Brain Pericyte cell line (TR-PCT) derived from the Brain capillary of a transgenic rat harboring a temperature-sensitive simian virus 40 T antigen gene. One of the clones was named TR-PCT1, and we established 6 clones of Pericyte-like cells from a 16 week-old tsA58 transgenic rat. For comparison, primary Pericytes from a Wistar rat were also studied. The expression of platelet-derived growth factor receptor beta, angiopoietin-1, osteopontin, and intercellular adhesion molecule-1 in TR-PCT1 was determined by reverse transcription-polymerase chain reaction. Transforming growth factor-beta1 enhanced a-smooth muscle actin expression in TR-PCT1, but this expression was reduced by subsequent treatment with basic fibroblast growth factor. When TR-PCT1 was seeded on type I collagen plates and treated with beta-glycerophosphate, nodules developed in the cells and these nodules reacted positively to von Kossa stain used as a marker of calcification. We believe that TR-PCT1 will help us gain a better understanding of the physiological and/or pathophysiological role of Pericytes.
Satoko Hori - One of the best experts on this subject based on the ideXlab platform.
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a Pericyte derived angiopoietin 1 multimeric complex induces occludin gene expression in Brain capillary endothelial cells through tie 2 activation in vitro
Journal of Neurochemistry, 2004Co-Authors: Satoko Hori, Sumio Ohtsuki, Kenichi Hosoya, Emi Nakashima, Tetsuya TerasakiAbstract:Although tight-junctions (TJs) at the blood-Brain barrier (BBB) are important to prevent non-specific entry of compounds into the CNS, molecular mechanisms regulating TJ maintenance remain still unclear. The purpose of this study was therefore to identify molecules, which regulate occludin expression, derived from astrocytes and Pericytes that ensheathe Brain microvessels by using conditionally immortalized adult rat Brain capillary endothelial (TR-BBB13), type II astrocyte (TR-AST4) and Brain Pericyte (TR-PCT1) cell lines. Transfilter co-culture with TR-AST4 cells, and exposure to conditioned medium of TR-AST4 cells (AST-CM) or TR-PCT1 cells (PCT-CM) increased occludin mRNA in TR-BBB13 cells. PCT-CM-induced occludin up-regulation was significantly inhibited by an angiopoietin-1-neutralizing antibody, whereas the up-regulation by AST-CM was not. Immunoprecipitation and western blot analyses confirmed that multimeric angiopoietin-1 is secreted from TR-PCT1 cells, and induces occludin mRNA, acting through tyrosine phosphorylation of Tie-2 in TR-BBB13 cells. A fractionated AST-CM study revealed that factors in the molecular weight range of 30-100 kDa led to occludin induction. Conversely, occludin mRNA was reduced by transforming growth factor beta 1, the mRNA of which was up-regulated in TR-AST4 cells following hypoxic treatment. In conclusion, in vitro BBB model studies revealed that the Pericyte-derived multimeric angiopoietin-1/Tie-2 pathway induces occludin expression.
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a Pericyte derived angiopoietin 1 multimeric complex induces occludin gene expression in Brain capillary endothelial cells through tie 2 activation in vitro
Journal of Neurochemistry, 2004Co-Authors: Satoko Hori, Sumio Ohtsuki, Kenichi Hosoya, Emi Nakashima, Tetsuya TerasakiAbstract:Although tight-junctions (TJs) at the blood–Brain barrier (BBB) are important to prevent non-specific entry of compounds into the CNS, molecular mechanisms regulating TJ maintenance remain still unclear. The purpose of this study was therefore to identify molecules, which regulate occludin expression, derived from astrocytes and Pericytes that ensheathe Brain microvessels by using conditionally immortalized adult rat Brain capillary endothelial (TR-BBB13), type II astrocyte (TR-AST4) and Brain Pericyte (TR-PCT1) cell lines. Transfilter co-culture with TR-AST4 cells, and exposure to conditioned medium of TR-AST4 cells (AST-CM) or TR-PCT1 cells (PCT-CM) increased occludin mRNA in TR-BBB13 cells. PCT-CM-induced occludin up-regulation was significantly inhibited by an angiopoietin-1-neutralizing antibody, whereas the up-regulation by AST-CM was not. Immunoprecipitation and western blot analyses confirmed that multimeric angiopoietin-1 is secreted from TR-PCT1 cells, and induces occludin mRNA, acting through tyrosine phosphorylation of Tie-2 in TR-BBB13 cells. A fractionated AST-CM study revealed that factors in the molecular weight range of 30–100 kDa led to occludin induction. Conversely, occludin mRNA was reduced by transforming growth factor β1, the mRNA of which was up-regulated in TR-AST4 cells following hypoxic treatment. In conclusion, in vitro BBB model studies revealed that the Pericyte-derived multimeric angiopoietin-1/Tie-2 pathway induces occludin expression.
Kenichi Hosoya - One of the best experts on this subject based on the ideXlab platform.
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a Pericyte derived angiopoietin 1 multimeric complex induces occludin gene expression in Brain capillary endothelial cells through tie 2 activation in vitro
Journal of Neurochemistry, 2004Co-Authors: Satoko Hori, Sumio Ohtsuki, Kenichi Hosoya, Emi Nakashima, Tetsuya TerasakiAbstract:Although tight-junctions (TJs) at the blood-Brain barrier (BBB) are important to prevent non-specific entry of compounds into the CNS, molecular mechanisms regulating TJ maintenance remain still unclear. The purpose of this study was therefore to identify molecules, which regulate occludin expression, derived from astrocytes and Pericytes that ensheathe Brain microvessels by using conditionally immortalized adult rat Brain capillary endothelial (TR-BBB13), type II astrocyte (TR-AST4) and Brain Pericyte (TR-PCT1) cell lines. Transfilter co-culture with TR-AST4 cells, and exposure to conditioned medium of TR-AST4 cells (AST-CM) or TR-PCT1 cells (PCT-CM) increased occludin mRNA in TR-BBB13 cells. PCT-CM-induced occludin up-regulation was significantly inhibited by an angiopoietin-1-neutralizing antibody, whereas the up-regulation by AST-CM was not. Immunoprecipitation and western blot analyses confirmed that multimeric angiopoietin-1 is secreted from TR-PCT1 cells, and induces occludin mRNA, acting through tyrosine phosphorylation of Tie-2 in TR-BBB13 cells. A fractionated AST-CM study revealed that factors in the molecular weight range of 30-100 kDa led to occludin induction. Conversely, occludin mRNA was reduced by transforming growth factor beta 1, the mRNA of which was up-regulated in TR-AST4 cells following hypoxic treatment. In conclusion, in vitro BBB model studies revealed that the Pericyte-derived multimeric angiopoietin-1/Tie-2 pathway induces occludin expression.
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a Pericyte derived angiopoietin 1 multimeric complex induces occludin gene expression in Brain capillary endothelial cells through tie 2 activation in vitro
Journal of Neurochemistry, 2004Co-Authors: Satoko Hori, Sumio Ohtsuki, Kenichi Hosoya, Emi Nakashima, Tetsuya TerasakiAbstract:Although tight-junctions (TJs) at the blood–Brain barrier (BBB) are important to prevent non-specific entry of compounds into the CNS, molecular mechanisms regulating TJ maintenance remain still unclear. The purpose of this study was therefore to identify molecules, which regulate occludin expression, derived from astrocytes and Pericytes that ensheathe Brain microvessels by using conditionally immortalized adult rat Brain capillary endothelial (TR-BBB13), type II astrocyte (TR-AST4) and Brain Pericyte (TR-PCT1) cell lines. Transfilter co-culture with TR-AST4 cells, and exposure to conditioned medium of TR-AST4 cells (AST-CM) or TR-PCT1 cells (PCT-CM) increased occludin mRNA in TR-BBB13 cells. PCT-CM-induced occludin up-regulation was significantly inhibited by an angiopoietin-1-neutralizing antibody, whereas the up-regulation by AST-CM was not. Immunoprecipitation and western blot analyses confirmed that multimeric angiopoietin-1 is secreted from TR-PCT1 cells, and induces occludin mRNA, acting through tyrosine phosphorylation of Tie-2 in TR-BBB13 cells. A fractionated AST-CM study revealed that factors in the molecular weight range of 30–100 kDa led to occludin induction. Conversely, occludin mRNA was reduced by transforming growth factor β1, the mRNA of which was up-regulated in TR-AST4 cells following hypoxic treatment. In conclusion, in vitro BBB model studies revealed that the Pericyte-derived multimeric angiopoietin-1/Tie-2 pathway induces occludin expression.
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newly developed rat Brain Pericyte cell line tr pct1 responds to transforming growth factor β1 and β glycerophosphate
European Journal of Cell Biology, 2002Co-Authors: Tomoko Asashima, Kenichi Hosoya, Tetsuya Terasaki, Hisashi Iizasa, Kazuhiro Tetsuka, Masatsugu Ueda, Masuo Obinata, Emi NakashimaAbstract:Brain Pericytes form an incomplete envelope around endothelial cells and within the microvascular basement membrane of capillaries and postcapillary venules. Recently, it has been reported that Brain Pericytes exhibit pluripotency, regulation of endothelial cell activity, and macrophage activity. However, many molecular and cellular aspects of Brain Pericytes remain unclear. In this study, we have tried to establish a conditionally immortalized Brain Pericyte cell line (TR-PCT) derived from the Brain capillary of a transgenic rat harboring a temperature-sensitive simian virus 40 T antigen gene. One of the clones was named TR-PCT1, and we established 6 clones of Pericyte-like cells from a 16 week-old tsA58 transgenic rat. For comparison, primary Pericytes from a Wistar rat were also studied. The expression of platelet-derived growth factor receptor beta, angiopoietin-1, osteopontin, and intercellular adhesion molecule-1 in TR-PCT1 was determined by reverse transcription-polymerase chain reaction. Transforming growth factor-beta1 enhanced a-smooth muscle actin expression in TR-PCT1, but this expression was reduced by subsequent treatment with basic fibroblast growth factor. When TR-PCT1 was seeded on type I collagen plates and treated with beta-glycerophosphate, nodules developed in the cells and these nodules reacted positively to von Kossa stain used as a marker of calcification. We believe that TR-PCT1 will help us gain a better understanding of the physiological and/or pathophysiological role of Pericytes.