Hepatic fibrogenesis and transforming growth factor/Smad signaling activation in rats chronically exposed to low doses of lead

Autores
Pérez Aguilar, Rossana Cristina; Honore, Stella Maris; Genta, Susana Beatriz de Fátima; Sanchez, Sara Serafina del V.
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Lead is an important heavy metal pollutant in the environment. The nervous system, kidney and liver are the most susceptible organs to lead deposition, showing that this pollutant has no single target system. To examine the cellular and molecular mechanisms involved in their pathobiology of chronic lead at low-dose exposure in the liver, male Wistar rats were exposed to 0.06% lead acetate in drinking water every day for 4 months. At the end of the study, hepatic metal accumulation, morphology and function were examined. Immunochemical staining and Western blot analysis were performed to detect extracellular matrix proteins, α-smooth muscle actin and transforming growth factor (TGF)β1/Smad pathway expression. Results showed increased laminin, collagen IV and fibronectin, located at the perisinusoidal space. Phenotypic transformation of hepatic stellate cells into myofibroblast-like cells was evidenced at the ultrastructural level and a significant expression of α-smooth muscle actin in Disse's space was observed. These findings were associated with a marked increase in TGFβ1/Smad2/3 signaling. Our data suggest that, chronically, exposure to low levels of lead could trigger the onset of a hepatic fibrogenic process through upregulated TGFβ1/Smad signaling.
Fil: Pérez Aguilar, Rossana Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina
Fil: Honore, Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina
Fil: Genta, Susana Beatriz de Fátima. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina
Fil: Sanchez, Sara Serafina del V.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina
Materia
Lead
Liver
Fibrogenesis
Tgf/Smad Signaling
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/31840
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/31840
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Hepatic fibrogenesis and transforming growth factor/Smad signaling activation in rats chronically exposed to low doses of leadPérez Aguilar, Rossana CristinaHonore, Stella MarisGenta, Susana Beatriz de FátimaSanchez, Sara Serafina del V.LeadLiverFibrogenesisTgf/Smad Signalinghttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Lead is an important heavy metal pollutant in the environment. The nervous system, kidney and liver are the most susceptible organs to lead deposition, showing that this pollutant has no single target system. To examine the cellular and molecular mechanisms involved in their pathobiology of chronic lead at low-dose exposure in the liver, male Wistar rats were exposed to 0.06% lead acetate in drinking water every day for 4 months. At the end of the study, hepatic metal accumulation, morphology and function were examined. Immunochemical staining and Western blot analysis were performed to detect extracellular matrix proteins, α-smooth muscle actin and transforming growth factor (TGF)β1/Smad pathway expression. Results showed increased laminin, collagen IV and fibronectin, located at the perisinusoidal space. Phenotypic transformation of hepatic stellate cells into myofibroblast-like cells was evidenced at the ultrastructural level and a significant expression of α-smooth muscle actin in Disse's space was observed. These findings were associated with a marked increase in TGFβ1/Smad2/3 signaling. Our data suggest that, chronically, exposure to low levels of lead could trigger the onset of a hepatic fibrogenic process through upregulated TGFβ1/Smad signaling.Fil: Pérez Aguilar, Rossana Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Honore, Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Genta, Susana Beatriz de Fátima. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Sanchez, Sara Serafina del V.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaWiley2013-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/31840Sanchez, Sara Serafina del V.; Genta, Susana Beatriz de Fátima; Honore, Stella Maris; Pérez Aguilar, Rossana Cristina; Hepatic fibrogenesis and transforming growth factor/Smad signaling activation in rats chronically exposed to low doses of lead; Wiley; Journal of Applied Toxicology; 34; 12; 11-2013; 1320-13310260-437XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/ 10.1002/jat.2955info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/jat.2955/abstractinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:36:39Zoai:ri.conicet.gov.ar:11336/31840instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 15:36:39.804CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Hepatic fibrogenesis and transforming growth factor/Smad signaling activation in rats chronically exposed to low doses of lead
title Hepatic fibrogenesis and transforming growth factor/Smad signaling activation in rats chronically exposed to low doses of lead
spellingShingle Hepatic fibrogenesis and transforming growth factor/Smad signaling activation in rats chronically exposed to low doses of lead
Pérez Aguilar, Rossana Cristina
Lead
Liver
Fibrogenesis
Tgf/Smad Signaling
title_short Hepatic fibrogenesis and transforming growth factor/Smad signaling activation in rats chronically exposed to low doses of lead
title_full Hepatic fibrogenesis and transforming growth factor/Smad signaling activation in rats chronically exposed to low doses of lead
title_fullStr Hepatic fibrogenesis and transforming growth factor/Smad signaling activation in rats chronically exposed to low doses of lead
title_full_unstemmed Hepatic fibrogenesis and transforming growth factor/Smad signaling activation in rats chronically exposed to low doses of lead
title_sort Hepatic fibrogenesis and transforming growth factor/Smad signaling activation in rats chronically exposed to low doses of lead
dc.creator.none.fl_str_mv Pérez Aguilar, Rossana Cristina
Honore, Stella Maris
Genta, Susana Beatriz de Fátima
Sanchez, Sara Serafina del V.
author Pérez Aguilar, Rossana Cristina
author_facet Pérez Aguilar, Rossana Cristina
Honore, Stella Maris
Genta, Susana Beatriz de Fátima
Sanchez, Sara Serafina del V.
author_role author
author2 Honore, Stella Maris
Genta, Susana Beatriz de Fátima
Sanchez, Sara Serafina del V.
author2_role author
author
author
dc.subject.none.fl_str_mv Lead
Liver
Fibrogenesis
Tgf/Smad Signaling
topic Lead
Liver
Fibrogenesis
Tgf/Smad Signaling
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Lead is an important heavy metal pollutant in the environment. The nervous system, kidney and liver are the most susceptible organs to lead deposition, showing that this pollutant has no single target system. To examine the cellular and molecular mechanisms involved in their pathobiology of chronic lead at low-dose exposure in the liver, male Wistar rats were exposed to 0.06% lead acetate in drinking water every day for 4 months. At the end of the study, hepatic metal accumulation, morphology and function were examined. Immunochemical staining and Western blot analysis were performed to detect extracellular matrix proteins, α-smooth muscle actin and transforming growth factor (TGF)β1/Smad pathway expression. Results showed increased laminin, collagen IV and fibronectin, located at the perisinusoidal space. Phenotypic transformation of hepatic stellate cells into myofibroblast-like cells was evidenced at the ultrastructural level and a significant expression of α-smooth muscle actin in Disse's space was observed. These findings were associated with a marked increase in TGFβ1/Smad2/3 signaling. Our data suggest that, chronically, exposure to low levels of lead could trigger the onset of a hepatic fibrogenic process through upregulated TGFβ1/Smad signaling.
Fil: Pérez Aguilar, Rossana Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina
Fil: Honore, Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina
Fil: Genta, Susana Beatriz de Fátima. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina
Fil: Sanchez, Sara Serafina del V.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina
description Lead is an important heavy metal pollutant in the environment. The nervous system, kidney and liver are the most susceptible organs to lead deposition, showing that this pollutant has no single target system. To examine the cellular and molecular mechanisms involved in their pathobiology of chronic lead at low-dose exposure in the liver, male Wistar rats were exposed to 0.06% lead acetate in drinking water every day for 4 months. At the end of the study, hepatic metal accumulation, morphology and function were examined. Immunochemical staining and Western blot analysis were performed to detect extracellular matrix proteins, α-smooth muscle actin and transforming growth factor (TGF)β1/Smad pathway expression. Results showed increased laminin, collagen IV and fibronectin, located at the perisinusoidal space. Phenotypic transformation of hepatic stellate cells into myofibroblast-like cells was evidenced at the ultrastructural level and a significant expression of α-smooth muscle actin in Disse's space was observed. These findings were associated with a marked increase in TGFβ1/Smad2/3 signaling. Our data suggest that, chronically, exposure to low levels of lead could trigger the onset of a hepatic fibrogenic process through upregulated TGFβ1/Smad signaling.
publishDate 2013
dc.date.none.fl_str_mv 2013-11
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/31840
Sanchez, Sara Serafina del V.; Genta, Susana Beatriz de Fátima; Honore, Stella Maris; Pérez Aguilar, Rossana Cristina; Hepatic fibrogenesis and transforming growth factor/Smad signaling activation in rats chronically exposed to low doses of lead; Wiley; Journal of Applied Toxicology; 34; 12; 11-2013; 1320-1331
0260-437X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/31840
identifier_str_mv Sanchez, Sara Serafina del V.; Genta, Susana Beatriz de Fátima; Honore, Stella Maris; Pérez Aguilar, Rossana Cristina; Hepatic fibrogenesis and transforming growth factor/Smad signaling activation in rats chronically exposed to low doses of lead; Wiley; Journal of Applied Toxicology; 34; 12; 11-2013; 1320-1331
0260-437X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/ 10.1002/jat.2955
info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/jat.2955/abstract
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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