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Karl Blirando - One of the best experts on this subject based on the ideXlab platform.
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slug a cancer related transcription factor is involved in vascular smooth muscle Cell Transdifferentiation induced by platelet derived growth factor bb during atherosclerosis
Journal of the American Heart Association, 2020Co-Authors: Nahema Ledard, Alexandrine Liboz, Bertrand Blondeau, Mégane Babiak, Célia Moulin, Benjamin Vallin, Isabelle Guillas, Véronique Mateo, Claire Jumeau, Karl BlirandoAbstract:Background Heart attacks and stroke often result from occlusive thrombi following the rupture of vulnerable atherosclerotic plaques. Vascular smooth muscle Cells (VSMCs) play a pivotal role in plaque vulnerability because of their switch towards a proinflammatory/macrophage-like phenotype when in the context of atherosclerosis. The prometastatic transcription factor Slug/Snail2 is a critical regulator of Cell phenotypic transition. Here, we aimed to investigate the role of Slug in the Transdifferentiation process of VSMCs occurring during atherogenesis. Methods and Results In rat and human primary aortic smooth muscle Cells, Slug protein expression is strongly and rapidly increased by platelet-derived growth factor-BB (PDGF-BB). PDGF-BB increases Slug protein without affecting mRNA levels indicating that this growth factor stabilizes Slug protein. Immunocytochemistry and subCellular fractionation experiments reveal that PDGF-BB triggers a rapid accumulation of Slug in VSMC nuclei. Using pharmacological tools, we show that the PDGF-BB-dependent mechanism of Slug stabilization in VSMCs involves the extraCellular signal-regulated kinase 1/2 pathway. Immunohistochemistry experiments on type V and type VI atherosclerotic lesions of human carotids show smooth muscle-specific myosin heavy chain-/Slug-positive Cells surrounding the prothrombotic lipid core. In VSMCs, Slug siRNAs inhibit prostaglandin E2 secretion and prevent the inhibition of cholesterol efflux gene expression mediated by PDGF-BB, known to be involved in plaque vulnerability and/or thrombogenicity. Conclusions Our results highlight, for the first time, a role of Slug in aortic smooth muscle Cell Transdifferentiation and enable us to consider Slug as an actor playing a role in the atherosclerotic plaque progression towards a life-threatening phenotype. This also argues for common features between acute cardiovascular events and cancer.
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Slug, a Cancer‐Related Transcription Factor, is Involved in Vascular Smooth Muscle Cell Transdifferentiation Induced by Platelet‐Derived Growth Factor‐BB During Atherosclerosis
Journal of the American Heart Association, 2020Co-Authors: Nahema Ledard, Alexandrine Liboz, Bertrand Blondeau, Mégane Babiak, Célia Moulin, Benjamin Vallin, Isabelle Guillas, Véronique Mateo, Claire Jumeau, Karl BlirandoAbstract:Background Heart attacks and stroke often result from occlusive thrombi following the rupture of vulnerable atherosclerotic plaques. Vascular smooth muscle Cells (VSMCs) play a pivotal role in plaque vulnerability because of their switch towards a proinflammatory/macrophage-like phenotype when in the context of atherosclerosis. The prometastatic transcription factor Slug/Snail2 is a critical regulator of Cell phenotypic transition. Here, we aimed to investigate the role of Slug in the Transdifferentiation process of VSMCs occurring during atherogenesis. Methods and Results In rat and human primary aortic smooth muscle Cells, Slug protein expression is strongly and rapidly increased by platelet-derived growth factor-BB (PDGF-BB). PDGF-BB increases Slug protein without affecting mRNA levels indicating that this growth factor stabilizes Slug protein. Immunocytochemistry and subCellular fractionation experiments reveal that PDGF-BB triggers a rapid accumulation of Slug in VSMC nuclei. Using pharmacological tools, we show that the PDGF-BB-dependent mechanism of Slug stabilization in VSMCs involves the extraCellular signal-regulated kinase 1/2 pathway. Immunohistochemistry experiments on type V and type VI atherosclerotic lesions of human carotids show smooth muscle-specific myosin heavy chain-/Slug-positive Cells surrounding the prothrombotic lipid core. In VSMCs, Slug siRNAs inhibit prostaglandin E2 secretion and prevent the inhibition of cholesterol efflux gene expression mediated by PDGF-BB, known to be involved in plaque vulnerability and/or thrombogenicity. Conclusions Our results highlight, for the first time, a role of Slug in aortic smooth muscle Cell Transdifferentiation and enable us to consider Slug as an actor playing a role in the atherosclerotic plaque progression towards a life-threatening phenotype. This also argues for common features between acute cardiovascular events and cancer.
Nahema Ledard - One of the best experts on this subject based on the ideXlab platform.
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slug a cancer related transcription factor is involved in vascular smooth muscle Cell Transdifferentiation induced by platelet derived growth factor bb during atherosclerosis
Journal of the American Heart Association, 2020Co-Authors: Nahema Ledard, Alexandrine Liboz, Bertrand Blondeau, Mégane Babiak, Célia Moulin, Benjamin Vallin, Isabelle Guillas, Véronique Mateo, Claire Jumeau, Karl BlirandoAbstract:Background Heart attacks and stroke often result from occlusive thrombi following the rupture of vulnerable atherosclerotic plaques. Vascular smooth muscle Cells (VSMCs) play a pivotal role in plaque vulnerability because of their switch towards a proinflammatory/macrophage-like phenotype when in the context of atherosclerosis. The prometastatic transcription factor Slug/Snail2 is a critical regulator of Cell phenotypic transition. Here, we aimed to investigate the role of Slug in the Transdifferentiation process of VSMCs occurring during atherogenesis. Methods and Results In rat and human primary aortic smooth muscle Cells, Slug protein expression is strongly and rapidly increased by platelet-derived growth factor-BB (PDGF-BB). PDGF-BB increases Slug protein without affecting mRNA levels indicating that this growth factor stabilizes Slug protein. Immunocytochemistry and subCellular fractionation experiments reveal that PDGF-BB triggers a rapid accumulation of Slug in VSMC nuclei. Using pharmacological tools, we show that the PDGF-BB-dependent mechanism of Slug stabilization in VSMCs involves the extraCellular signal-regulated kinase 1/2 pathway. Immunohistochemistry experiments on type V and type VI atherosclerotic lesions of human carotids show smooth muscle-specific myosin heavy chain-/Slug-positive Cells surrounding the prothrombotic lipid core. In VSMCs, Slug siRNAs inhibit prostaglandin E2 secretion and prevent the inhibition of cholesterol efflux gene expression mediated by PDGF-BB, known to be involved in plaque vulnerability and/or thrombogenicity. Conclusions Our results highlight, for the first time, a role of Slug in aortic smooth muscle Cell Transdifferentiation and enable us to consider Slug as an actor playing a role in the atherosclerotic plaque progression towards a life-threatening phenotype. This also argues for common features between acute cardiovascular events and cancer.
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Slug, a Cancer‐Related Transcription Factor, is Involved in Vascular Smooth Muscle Cell Transdifferentiation Induced by Platelet‐Derived Growth Factor‐BB During Atherosclerosis
Journal of the American Heart Association, 2020Co-Authors: Nahema Ledard, Alexandrine Liboz, Bertrand Blondeau, Mégane Babiak, Célia Moulin, Benjamin Vallin, Isabelle Guillas, Véronique Mateo, Claire Jumeau, Karl BlirandoAbstract:Background Heart attacks and stroke often result from occlusive thrombi following the rupture of vulnerable atherosclerotic plaques. Vascular smooth muscle Cells (VSMCs) play a pivotal role in plaque vulnerability because of their switch towards a proinflammatory/macrophage-like phenotype when in the context of atherosclerosis. The prometastatic transcription factor Slug/Snail2 is a critical regulator of Cell phenotypic transition. Here, we aimed to investigate the role of Slug in the Transdifferentiation process of VSMCs occurring during atherogenesis. Methods and Results In rat and human primary aortic smooth muscle Cells, Slug protein expression is strongly and rapidly increased by platelet-derived growth factor-BB (PDGF-BB). PDGF-BB increases Slug protein without affecting mRNA levels indicating that this growth factor stabilizes Slug protein. Immunocytochemistry and subCellular fractionation experiments reveal that PDGF-BB triggers a rapid accumulation of Slug in VSMC nuclei. Using pharmacological tools, we show that the PDGF-BB-dependent mechanism of Slug stabilization in VSMCs involves the extraCellular signal-regulated kinase 1/2 pathway. Immunohistochemistry experiments on type V and type VI atherosclerotic lesions of human carotids show smooth muscle-specific myosin heavy chain-/Slug-positive Cells surrounding the prothrombotic lipid core. In VSMCs, Slug siRNAs inhibit prostaglandin E2 secretion and prevent the inhibition of cholesterol efflux gene expression mediated by PDGF-BB, known to be involved in plaque vulnerability and/or thrombogenicity. Conclusions Our results highlight, for the first time, a role of Slug in aortic smooth muscle Cell Transdifferentiation and enable us to consider Slug as an actor playing a role in the atherosclerotic plaque progression towards a life-threatening phenotype. This also argues for common features between acute cardiovascular events and cancer.
Ivo Gut - One of the best experts on this subject based on the ideXlab platform.
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Single Cell RNA-seq identifies the origins of heterogeneity in efficient Cell Transdifferentiation and reprogramming.
eLife, 2019Co-Authors: Mirko Francesconi, Clara Berenguer, Bruno Di Stefano, Luisa De Andrés-aguayo, Marcos Plana-carmona, Maria Mendez Lago, Amy Guillaumet-adkins, Gustavo Rodríguez-esteban, Marta Gut, Ivo GutAbstract:Forced transcription factor expression can transdifferentiate somatic Cells into other specialised Cell types or reprogram them into induced pluripotent stem Cells (iPSCs) with variable efficiency. To better understand the heterogeneity of these processes, we used single-Cell RNA sequencing to follow the transdifferentation of murine pre-B Cells into macrophages as well as their reprogramming into iPSCs. Even in these highly efficient systems, there was substantial variation in the speed and path of fate conversion. We predicted and validated that these differences are inversely coupled and arise in the starting Cell population, with Mychigh large pre-BII Cells transdifferentiating slowly but reprogramming efficiently and Myclow small pre-BII Cells transdifferentiating rapidly but failing to reprogram. Strikingly, differences in Myc activity predict the efficiency of reprogramming across a wide range of somatic Cell types. These results illustrate how single Cell expression and computational analyses can identify the origins of heterogeneity in Cell fate conversion processes.
Alain Meyrier - One of the best experts on this subject based on the ideXlab platform.
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Transdifferentiation of epithelial glomerular Cells.
Journal of The American Society of Nephrology, 2003Co-Authors: Jean Bariety, Patrick Bruneval, Gary S. Hill, Chantal Mandet, Christian Jacquot, Alain MeyrierAbstract:Cell Transdifferentiation is characterized by loss of some phenotypes along with acquisition of new phenotypes in differentiated Cells. Differentiated Cells are endowed with the capacity of transforming into Cells of a different type having other functions ([1,2][1][⇓][2]). Gene expression in
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Posttransplantation Relapse of FSGS Is Characterized by Glomerular Epithelial Cell Transdifferentiation
Journal of the American Society of Nephrology : JASN, 2001Co-Authors: Jean Bariety, Patrick Bruneval, Gary S. Hill, Chantal Mandet, Theano Irinopoulou, Alain MeyrierAbstract:This study examined six cases of idiopathic nephrotic syndrome with primary lesions of focal segmental glomerulosclerosis (FSGS) that relapsed after renal transplantation. The glomerular lesions comprised the Cellular, the collapsing, and the scar variants of FSGS and showed shedding of large round Cells into Bowman's space and within the tubular lumens. Immunohistochemistry and confocal laser microscopy carried out on kidneys with FSGS relapse disclosed several phenomena. (1) Some podocytes that expressed podocalyxin, synaptopodin, and glomerular epithelial protein-1 were detached from the tuft and were free in the urinary space. (2) In the Cellular variant, most podocytes had lost podocyte-specific epitopes (podocalyxin, synaptopodin, glomerular epithelial protein-1, Wilm's tumor protein-1, complement receptor-1, and vimentin). In the scar variant, these podocyte markers were absent from cobblestone-like epithelial Cells and from pseudotubules. (3) Podocytes had acquired expression of various cytokeratins (CK; identified by the AE1/AE3, C2562, CK22, and AEL-KS2 monoclonal antibodies) that were not found in the podocytes of control glomeruli. Parietal epithelial Cells expressed AE1/AE3 CK that were faintly, if ever, found on the parietal epithelial Cells of normal glomeruli. (4) Numerous Cells located at the periphery of the tuft or free in Bowman's space and within tubular lumens expressed macrophagic epitopes (identified by PGM1 [CD68], HAM56, and 25F9 monoclonal antibodies). These macrophage-like Cells expressed the activation epitopes HLA-DR and CD16. (5) A number of these Cells coexpressed podocalyxin + AE1/AE3 CK, podocalyxin + CD68, and CD68 + AE1/AE3. These findings suggest that in primary FSGS relapsing on transplanted kidneys, some "dysregulated" podocytes, occasionally some parietal epithelial Cells, and possibly some tubular epithelial Cells undergo a process of Transdifferentiation. This process of Transdifferentiation was especially striking in podocytes that acquired macrophagic and CK epitopes that are absent from normal adult and fetal podocytes.
Alexandrine Liboz - One of the best experts on this subject based on the ideXlab platform.
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slug a cancer related transcription factor is involved in vascular smooth muscle Cell Transdifferentiation induced by platelet derived growth factor bb during atherosclerosis
Journal of the American Heart Association, 2020Co-Authors: Nahema Ledard, Alexandrine Liboz, Bertrand Blondeau, Mégane Babiak, Célia Moulin, Benjamin Vallin, Isabelle Guillas, Véronique Mateo, Claire Jumeau, Karl BlirandoAbstract:Background Heart attacks and stroke often result from occlusive thrombi following the rupture of vulnerable atherosclerotic plaques. Vascular smooth muscle Cells (VSMCs) play a pivotal role in plaque vulnerability because of their switch towards a proinflammatory/macrophage-like phenotype when in the context of atherosclerosis. The prometastatic transcription factor Slug/Snail2 is a critical regulator of Cell phenotypic transition. Here, we aimed to investigate the role of Slug in the Transdifferentiation process of VSMCs occurring during atherogenesis. Methods and Results In rat and human primary aortic smooth muscle Cells, Slug protein expression is strongly and rapidly increased by platelet-derived growth factor-BB (PDGF-BB). PDGF-BB increases Slug protein without affecting mRNA levels indicating that this growth factor stabilizes Slug protein. Immunocytochemistry and subCellular fractionation experiments reveal that PDGF-BB triggers a rapid accumulation of Slug in VSMC nuclei. Using pharmacological tools, we show that the PDGF-BB-dependent mechanism of Slug stabilization in VSMCs involves the extraCellular signal-regulated kinase 1/2 pathway. Immunohistochemistry experiments on type V and type VI atherosclerotic lesions of human carotids show smooth muscle-specific myosin heavy chain-/Slug-positive Cells surrounding the prothrombotic lipid core. In VSMCs, Slug siRNAs inhibit prostaglandin E2 secretion and prevent the inhibition of cholesterol efflux gene expression mediated by PDGF-BB, known to be involved in plaque vulnerability and/or thrombogenicity. Conclusions Our results highlight, for the first time, a role of Slug in aortic smooth muscle Cell Transdifferentiation and enable us to consider Slug as an actor playing a role in the atherosclerotic plaque progression towards a life-threatening phenotype. This also argues for common features between acute cardiovascular events and cancer.
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Slug, a Cancer‐Related Transcription Factor, is Involved in Vascular Smooth Muscle Cell Transdifferentiation Induced by Platelet‐Derived Growth Factor‐BB During Atherosclerosis
Journal of the American Heart Association, 2020Co-Authors: Nahema Ledard, Alexandrine Liboz, Bertrand Blondeau, Mégane Babiak, Célia Moulin, Benjamin Vallin, Isabelle Guillas, Véronique Mateo, Claire Jumeau, Karl BlirandoAbstract:Background Heart attacks and stroke often result from occlusive thrombi following the rupture of vulnerable atherosclerotic plaques. Vascular smooth muscle Cells (VSMCs) play a pivotal role in plaque vulnerability because of their switch towards a proinflammatory/macrophage-like phenotype when in the context of atherosclerosis. The prometastatic transcription factor Slug/Snail2 is a critical regulator of Cell phenotypic transition. Here, we aimed to investigate the role of Slug in the Transdifferentiation process of VSMCs occurring during atherogenesis. Methods and Results In rat and human primary aortic smooth muscle Cells, Slug protein expression is strongly and rapidly increased by platelet-derived growth factor-BB (PDGF-BB). PDGF-BB increases Slug protein without affecting mRNA levels indicating that this growth factor stabilizes Slug protein. Immunocytochemistry and subCellular fractionation experiments reveal that PDGF-BB triggers a rapid accumulation of Slug in VSMC nuclei. Using pharmacological tools, we show that the PDGF-BB-dependent mechanism of Slug stabilization in VSMCs involves the extraCellular signal-regulated kinase 1/2 pathway. Immunohistochemistry experiments on type V and type VI atherosclerotic lesions of human carotids show smooth muscle-specific myosin heavy chain-/Slug-positive Cells surrounding the prothrombotic lipid core. In VSMCs, Slug siRNAs inhibit prostaglandin E2 secretion and prevent the inhibition of cholesterol efflux gene expression mediated by PDGF-BB, known to be involved in plaque vulnerability and/or thrombogenicity. Conclusions Our results highlight, for the first time, a role of Slug in aortic smooth muscle Cell Transdifferentiation and enable us to consider Slug as an actor playing a role in the atherosclerotic plaque progression towards a life-threatening phenotype. This also argues for common features between acute cardiovascular events and cancer.