Regulation of fibronectin splicing in sinusoidal endothelial cells from normal or injured liver

Fn containing an extra type III domain (EIIIA in the rat, ED1 or EDA in humans) is commonly termed "fetal" fibronectin, but it is prominent during the injury response of adult tissues and mediates important early events in the response. This form is particularly apparent in acute liver inj...

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Autores principales:	Alonso, Claudio Roberto, Kornblihtt, Alberto Rodolfo
Publicado:	2004
Materias:	Extracellular matrix Fibrosis Spliceosome TGFβ fibronectin transforming growth factor beta transforming growth factor beta receptor alternative RNA splicing animal cell animal experiment animal model article cell growth controlled study endothelium cell extracellular matrix genetic transfection HeLa cell liver histology liver injury male nonhuman priority journal promoter region rat reporter gene reverse transcription polymerase chain reaction spliceosome Alternative Splicing Animals Cell Line Cell Line, Tumor Endothelium Fibronectins Genes, Reporter Hela Cells Humans Introns Liver Male Mice Models, Genetic Plasmids Promoter Regions (Genetics) Protein Structure, Tertiary Rats Rats, Wistar Receptors, Transforming Growth Factor beta Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger Signal Transduction Spliceosomes Time Factors Transfection Transforming Growth Factor beta Animalia
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00278424_v101_n52_p18093_Chang http://hdl.handle.net/20.500.12110/paper_00278424_v101_n52_p18093_Chang
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	paper:paper_00278424_v101_n52_p18093_Chang2023-06-08T14:54:20Z Regulation of fibronectin splicing in sinusoidal endothelial cells from normal or injured liver Alonso, Claudio Roberto Kornblihtt, Alberto Rodolfo Extracellular matrix Fibrosis Spliceosome TGFβ fibronectin transforming growth factor beta transforming growth factor beta receptor alternative RNA splicing animal cell animal experiment animal model article cell growth controlled study endothelium cell extracellular matrix genetic transfection HeLa cell liver histology liver injury male nonhuman priority journal promoter region rat reporter gene reverse transcription polymerase chain reaction spliceosome Alternative Splicing Animals Cell Line Cell Line, Tumor Endothelium Fibronectins Genes, Reporter Hela Cells Humans Introns Liver Male Mice Models, Genetic Plasmids Promoter Regions (Genetics) Protein Structure, Tertiary Rats Rats, Wistar Receptors, Transforming Growth Factor beta Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger Signal Transduction Spliceosomes Time Factors Transfection Transforming Growth Factor beta Animalia Fn containing an extra type III domain (EIIIA in the rat, ED1 or EDA in humans) is commonly termed "fetal" fibronectin, but it is prominent during the injury response of adult tissues and mediates important early events in the response. This form is particularly apparent in acute liver injury, where it has been shown that sinusoidal endothelial cells produce EIIIA-fibronectin. This fibronectin isoform arises by alternative splicing of the primary transcript. In the present experiments, we have studied the regulation of fibronectin splicing in primary sinusoidal endothelial cells by transfecting a minigene containing the EIIIA exon and its flanking introns, driven by various promoters. The results indicate that fibronectin splicing in endothelial cells from normal liver is in part promoter-dependent. However, in cells from injured liver in which expression of both total and EIIIA-fibronectin is strikingly increased, promoter effects disappear. Because fibronectin splicing is known to be regulated in part by TGFβ, we also examined the effect of a soluble inhibitor of the TGFβ type 2 receptor. This agent had no effect on splicing by normal endothelial cells. By contrast, for endothelial cells from the injured liver, the splicing pattern reverted to that of normal cells, i.e., it became promoter-dependent. We conclude that, in the setting of injury in vivo, TGFβ overrides the promoter dependence of fibronectin splicing in normal cells. The data suggest that TGFβ modifies the spliceosome, if not through its known signaling intermediates, then through the products of genes regulated by this cytokine. Fil:Alonso, C.R. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Kornblihtt, A.R. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2004 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00278424_v101_n52_p18093_Chang http://hdl.handle.net/20.500.12110/paper_00278424_v101_n52_p18093_Chang
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Extracellular matrix Fibrosis Spliceosome TGFβ fibronectin transforming growth factor beta transforming growth factor beta receptor alternative RNA splicing animal cell animal experiment animal model article cell growth controlled study endothelium cell extracellular matrix genetic transfection HeLa cell liver histology liver injury male nonhuman priority journal promoter region rat reporter gene reverse transcription polymerase chain reaction spliceosome Alternative Splicing Animals Cell Line Cell Line, Tumor Endothelium Fibronectins Genes, Reporter Hela Cells Humans Introns Liver Male Mice Models, Genetic Plasmids Promoter Regions (Genetics) Protein Structure, Tertiary Rats Rats, Wistar Receptors, Transforming Growth Factor beta Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger Signal Transduction Spliceosomes Time Factors Transfection Transforming Growth Factor beta Animalia
spellingShingle	Extracellular matrix Fibrosis Spliceosome TGFβ fibronectin transforming growth factor beta transforming growth factor beta receptor alternative RNA splicing animal cell animal experiment animal model article cell growth controlled study endothelium cell extracellular matrix genetic transfection HeLa cell liver histology liver injury male nonhuman priority journal promoter region rat reporter gene reverse transcription polymerase chain reaction spliceosome Alternative Splicing Animals Cell Line Cell Line, Tumor Endothelium Fibronectins Genes, Reporter Hela Cells Humans Introns Liver Male Mice Models, Genetic Plasmids Promoter Regions (Genetics) Protein Structure, Tertiary Rats Rats, Wistar Receptors, Transforming Growth Factor beta Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger Signal Transduction Spliceosomes Time Factors Transfection Transforming Growth Factor beta Animalia Alonso, Claudio Roberto Kornblihtt, Alberto Rodolfo Regulation of fibronectin splicing in sinusoidal endothelial cells from normal or injured liver
topic_facet	Extracellular matrix Fibrosis Spliceosome TGFβ fibronectin transforming growth factor beta transforming growth factor beta receptor alternative RNA splicing animal cell animal experiment animal model article cell growth controlled study endothelium cell extracellular matrix genetic transfection HeLa cell liver histology liver injury male nonhuman priority journal promoter region rat reporter gene reverse transcription polymerase chain reaction spliceosome Alternative Splicing Animals Cell Line Cell Line, Tumor Endothelium Fibronectins Genes, Reporter Hela Cells Humans Introns Liver Male Mice Models, Genetic Plasmids Promoter Regions (Genetics) Protein Structure, Tertiary Rats Rats, Wistar Receptors, Transforming Growth Factor beta Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger Signal Transduction Spliceosomes Time Factors Transfection Transforming Growth Factor beta Animalia
description	Fn containing an extra type III domain (EIIIA in the rat, ED1 or EDA in humans) is commonly termed "fetal" fibronectin, but it is prominent during the injury response of adult tissues and mediates important early events in the response. This form is particularly apparent in acute liver injury, where it has been shown that sinusoidal endothelial cells produce EIIIA-fibronectin. This fibronectin isoform arises by alternative splicing of the primary transcript. In the present experiments, we have studied the regulation of fibronectin splicing in primary sinusoidal endothelial cells by transfecting a minigene containing the EIIIA exon and its flanking introns, driven by various promoters. The results indicate that fibronectin splicing in endothelial cells from normal liver is in part promoter-dependent. However, in cells from injured liver in which expression of both total and EIIIA-fibronectin is strikingly increased, promoter effects disappear. Because fibronectin splicing is known to be regulated in part by TGFβ, we also examined the effect of a soluble inhibitor of the TGFβ type 2 receptor. This agent had no effect on splicing by normal endothelial cells. By contrast, for endothelial cells from the injured liver, the splicing pattern reverted to that of normal cells, i.e., it became promoter-dependent. We conclude that, in the setting of injury in vivo, TGFβ overrides the promoter dependence of fibronectin splicing in normal cells. The data suggest that TGFβ modifies the spliceosome, if not through its known signaling intermediates, then through the products of genes regulated by this cytokine.
author	Alonso, Claudio Roberto Kornblihtt, Alberto Rodolfo
author_facet	Alonso, Claudio Roberto Kornblihtt, Alberto Rodolfo
author_sort	Alonso, Claudio Roberto
title	Regulation of fibronectin splicing in sinusoidal endothelial cells from normal or injured liver
title_short	Regulation of fibronectin splicing in sinusoidal endothelial cells from normal or injured liver
title_full	Regulation of fibronectin splicing in sinusoidal endothelial cells from normal or injured liver
title_fullStr	Regulation of fibronectin splicing in sinusoidal endothelial cells from normal or injured liver
title_full_unstemmed	Regulation of fibronectin splicing in sinusoidal endothelial cells from normal or injured liver
title_sort	regulation of fibronectin splicing in sinusoidal endothelial cells from normal or injured liver
publishDate	2004
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00278424_v101_n52_p18093_Chang http://hdl.handle.net/20.500.12110/paper_00278424_v101_n52_p18093_Chang
work_keys_str_mv	AT alonsoclaudioroberto regulationoffibronectinsplicinginsinusoidalendothelialcellsfromnormalorinjuredliver AT kornblihttalbertorodolfo regulationoffibronectinsplicinginsinusoidalendothelialcellsfromnormalorinjuredliver
_version_	1768543598132854784

Regulation of fibronectin splicing in sinusoidal endothelial cells from normal or injured liver

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