Mitogenic signaling pathways in the liver of growth hormone (GH)-overexpressing mice during the growth period

Autores
Martinez, Carolina Soledad; Piazza, Verónica Gabriela; Gonzalez, Lorena; Fang, Yimin; Bartke, Andrzej; Turyn, Daniel; Miquet, Johanna Gabriela; Sotelo, Ana Isabel
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
ABSTRACT: Growth hormone (GH) is a pleiotropic hormone that triggers STATs, ERK1/2 and Akt signaling, related to cell growth and proliferation. Transgenic mice overexpressing GH present increased body size, with a disproportionate liver enlargement due to hypertrophy and hyperplasia of the hepatocytes. We had described enhanced mitogenic signaling in liver of young adult transgenic mice. We now evaluate the activation of these signaling cascades during the growth period and relate them to the morphological alterations found. Signaling mediators, cell cycle regulators and transcription factors involved in cellular growth in the liver of GH-overexpressing growing mice were assessed by immunoblotting, RT-qPCR and immunohistochemistry. Hepatocyte enlargement can be seen as early as 2-weeks of age in GH-overexpressing animals, although it is more pronounced in young adults. Levels of cell cycle mediators PCNA and cyclin D1, and transcription factor c-Jun increase with age in transgenic mice with no changes in normal mice, whereas c-Myc levels are higher in 2-week-old transgenic animals and cyclin E levels decline with age for both genotypes. STAT3, Akt and GSK3 present higher activation in the adult transgenic mice than in the growing animals, while for c-Src and mTOR, phosphorylation in GH-overexpressing mice is higher than in control siblings at 4 and 9 weeks of age. No significant changes are observed for ERK1/2, neither by age or genotype. Thus, the majority of the mitogenic signaling pathways are gradually up-regulated in the liver of GH-transgenic mice, giving rise to the hepatic morphological changes these mice exhibit.
Fil: Martinez, Carolina Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas ; Argentina
Fil: Piazza, Verónica Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas ; Argentina
Fil: Gonzalez, Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas ; Argentina
Fil: Fang, Yimin. Southern Illinois University; Estados Unidos
Fil: Bartke, Andrzej. Southern Illinois University; Estados Unidos
Fil: Turyn, Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas ; Argentina
Fil: Miquet, Johanna Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas ; Argentina
Fil: Sotelo, Ana Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas ; Argentina
Materia
Akt/Mtor/Gsk3β
C-Jun
C-Myc
Cell Cycle Regulators
Erk1/2
Gh-Overexpressing Mice
Growth Hormone
Hepatomegaly
Liver
Pcna
Stat3
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:11336/40334
Acceder
id CONICETDig_324b7b5301e09bb5c840e670ee544048
oai_identifier_str oai:ri.conicet.gov.ar:11336/40334
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Mitogenic signaling pathways in the liver of growth hormone (GH)-overexpressing mice during the growth periodMartinez, Carolina SoledadPiazza, Verónica GabrielaGonzalez, LorenaFang, YiminBartke, AndrzejTuryn, DanielMiquet, Johanna GabrielaSotelo, Ana IsabelAkt/Mtor/Gsk3βC-JunC-MycCell Cycle RegulatorsErk1/2Gh-Overexpressing MiceGrowth HormoneHepatomegalyLiverPcnaStat3https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1ABSTRACT: Growth hormone (GH) is a pleiotropic hormone that triggers STATs, ERK1/2 and Akt signaling, related to cell growth and proliferation. Transgenic mice overexpressing GH present increased body size, with a disproportionate liver enlargement due to hypertrophy and hyperplasia of the hepatocytes. We had described enhanced mitogenic signaling in liver of young adult transgenic mice. We now evaluate the activation of these signaling cascades during the growth period and relate them to the morphological alterations found. Signaling mediators, cell cycle regulators and transcription factors involved in cellular growth in the liver of GH-overexpressing growing mice were assessed by immunoblotting, RT-qPCR and immunohistochemistry. Hepatocyte enlargement can be seen as early as 2-weeks of age in GH-overexpressing animals, although it is more pronounced in young adults. Levels of cell cycle mediators PCNA and cyclin D1, and transcription factor c-Jun increase with age in transgenic mice with no changes in normal mice, whereas c-Myc levels are higher in 2-week-old transgenic animals and cyclin E levels decline with age for both genotypes. STAT3, Akt and GSK3 present higher activation in the adult transgenic mice than in the growing animals, while for c-Src and mTOR, phosphorylation in GH-overexpressing mice is higher than in control siblings at 4 and 9 weeks of age. No significant changes are observed for ERK1/2, neither by age or genotype. Thus, the majority of the mitogenic signaling pathways are gradually up-regulated in the liver of GH-transgenic mice, giving rise to the hepatic morphological changes these mice exhibit.Fil: Martinez, Carolina Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas ; ArgentinaFil: Piazza, Verónica Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas ; ArgentinaFil: Gonzalez, Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas ; ArgentinaFil: Fang, Yimin. Southern Illinois University; Estados UnidosFil: Bartke, Andrzej. Southern Illinois University; Estados UnidosFil: Turyn, Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas ; ArgentinaFil: Miquet, Johanna Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas ; ArgentinaFil: Sotelo, Ana Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas ; ArgentinaTaylor & Francis2016-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/40334Martinez, Carolina Soledad; Piazza, Verónica Gabriela; Gonzalez, Lorena; Fang, Yimin; Bartke, Andrzej; et al.; Mitogenic signaling pathways in the liver of growth hormone (GH)-overexpressing mice during the growth period; Taylor & Francis; Cell Cycle; 15; 5; 3-2016; 748-7591538-4101CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.tandfonline.com/doi/full/10.1080/15384101.2016.1148844info:eu-repo/semantics/altIdentifier/doi/10.1080/15384101.2016.1148844info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:45:08Zoai:ri.conicet.gov.ar:11336/40334instacron: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:34982025-09-03 09:45:08.365CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Mitogenic signaling pathways in the liver of growth hormone (GH)-overexpressing mice during the growth period
title Mitogenic signaling pathways in the liver of growth hormone (GH)-overexpressing mice during the growth period
spellingShingle Mitogenic signaling pathways in the liver of growth hormone (GH)-overexpressing mice during the growth period
Martinez, Carolina Soledad
Akt/Mtor/Gsk3β
C-Jun
C-Myc
Cell Cycle Regulators
Erk1/2
Gh-Overexpressing Mice
Growth Hormone
Hepatomegaly
Liver
Pcna
Stat3
title_short Mitogenic signaling pathways in the liver of growth hormone (GH)-overexpressing mice during the growth period
title_full Mitogenic signaling pathways in the liver of growth hormone (GH)-overexpressing mice during the growth period
title_fullStr Mitogenic signaling pathways in the liver of growth hormone (GH)-overexpressing mice during the growth period
title_full_unstemmed Mitogenic signaling pathways in the liver of growth hormone (GH)-overexpressing mice during the growth period
title_sort Mitogenic signaling pathways in the liver of growth hormone (GH)-overexpressing mice during the growth period
dc.creator.none.fl_str_mv Martinez, Carolina Soledad
Piazza, Verónica Gabriela
Gonzalez, Lorena
Fang, Yimin
Bartke, Andrzej
Turyn, Daniel
Miquet, Johanna Gabriela
Sotelo, Ana Isabel
author Martinez, Carolina Soledad
author_facet Martinez, Carolina Soledad
Piazza, Verónica Gabriela
Gonzalez, Lorena
Fang, Yimin
Bartke, Andrzej
Turyn, Daniel
Miquet, Johanna Gabriela
Sotelo, Ana Isabel
author_role author
author2 Piazza, Verónica Gabriela
Gonzalez, Lorena
Fang, Yimin
Bartke, Andrzej
Turyn, Daniel
Miquet, Johanna Gabriela
Sotelo, Ana Isabel
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Akt/Mtor/Gsk3β
C-Jun
C-Myc
Cell Cycle Regulators
Erk1/2
Gh-Overexpressing Mice
Growth Hormone
Hepatomegaly
Liver
Pcna
Stat3
topic Akt/Mtor/Gsk3β
C-Jun
C-Myc
Cell Cycle Regulators
Erk1/2
Gh-Overexpressing Mice
Growth Hormone
Hepatomegaly
Liver
Pcna
Stat3
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv ABSTRACT: Growth hormone (GH) is a pleiotropic hormone that triggers STATs, ERK1/2 and Akt signaling, related to cell growth and proliferation. Transgenic mice overexpressing GH present increased body size, with a disproportionate liver enlargement due to hypertrophy and hyperplasia of the hepatocytes. We had described enhanced mitogenic signaling in liver of young adult transgenic mice. We now evaluate the activation of these signaling cascades during the growth period and relate them to the morphological alterations found. Signaling mediators, cell cycle regulators and transcription factors involved in cellular growth in the liver of GH-overexpressing growing mice were assessed by immunoblotting, RT-qPCR and immunohistochemistry. Hepatocyte enlargement can be seen as early as 2-weeks of age in GH-overexpressing animals, although it is more pronounced in young adults. Levels of cell cycle mediators PCNA and cyclin D1, and transcription factor c-Jun increase with age in transgenic mice with no changes in normal mice, whereas c-Myc levels are higher in 2-week-old transgenic animals and cyclin E levels decline with age for both genotypes. STAT3, Akt and GSK3 present higher activation in the adult transgenic mice than in the growing animals, while for c-Src and mTOR, phosphorylation in GH-overexpressing mice is higher than in control siblings at 4 and 9 weeks of age. No significant changes are observed for ERK1/2, neither by age or genotype. Thus, the majority of the mitogenic signaling pathways are gradually up-regulated in the liver of GH-transgenic mice, giving rise to the hepatic morphological changes these mice exhibit.
Fil: Martinez, Carolina Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas ; Argentina
Fil: Piazza, Verónica Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas ; Argentina
Fil: Gonzalez, Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas ; Argentina
Fil: Fang, Yimin. Southern Illinois University; Estados Unidos
Fil: Bartke, Andrzej. Southern Illinois University; Estados Unidos
Fil: Turyn, Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas ; Argentina
Fil: Miquet, Johanna Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas ; Argentina
Fil: Sotelo, Ana Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas ; Argentina
description ABSTRACT: Growth hormone (GH) is a pleiotropic hormone that triggers STATs, ERK1/2 and Akt signaling, related to cell growth and proliferation. Transgenic mice overexpressing GH present increased body size, with a disproportionate liver enlargement due to hypertrophy and hyperplasia of the hepatocytes. We had described enhanced mitogenic signaling in liver of young adult transgenic mice. We now evaluate the activation of these signaling cascades during the growth period and relate them to the morphological alterations found. Signaling mediators, cell cycle regulators and transcription factors involved in cellular growth in the liver of GH-overexpressing growing mice were assessed by immunoblotting, RT-qPCR and immunohistochemistry. Hepatocyte enlargement can be seen as early as 2-weeks of age in GH-overexpressing animals, although it is more pronounced in young adults. Levels of cell cycle mediators PCNA and cyclin D1, and transcription factor c-Jun increase with age in transgenic mice with no changes in normal mice, whereas c-Myc levels are higher in 2-week-old transgenic animals and cyclin E levels decline with age for both genotypes. STAT3, Akt and GSK3 present higher activation in the adult transgenic mice than in the growing animals, while for c-Src and mTOR, phosphorylation in GH-overexpressing mice is higher than in control siblings at 4 and 9 weeks of age. No significant changes are observed for ERK1/2, neither by age or genotype. Thus, the majority of the mitogenic signaling pathways are gradually up-regulated in the liver of GH-transgenic mice, giving rise to the hepatic morphological changes these mice exhibit.
publishDate 2016
dc.date.none.fl_str_mv 2016-03
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/11336/40334
Martinez, Carolina Soledad; Piazza, Verónica Gabriela; Gonzalez, Lorena; Fang, Yimin; Bartke, Andrzej; et al.; Mitogenic signaling pathways in the liver of growth hormone (GH)-overexpressing mice during the growth period; Taylor & Francis; Cell Cycle; 15; 5; 3-2016; 748-759
1538-4101
CONICET Digital
CONICET
url http://hdl.handle.net/11336/40334
identifier_str_mv Martinez, Carolina Soledad; Piazza, Verónica Gabriela; Gonzalez, Lorena; Fang, Yimin; Bartke, Andrzej; et al.; Mitogenic signaling pathways in the liver of growth hormone (GH)-overexpressing mice during the growth period; Taylor & Francis; Cell Cycle; 15; 5; 3-2016; 748-759
1538-4101
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.tandfonline.com/doi/full/10.1080/15384101.2016.1148844
info:eu-repo/semantics/altIdentifier/doi/10.1080/15384101.2016.1148844
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
application/pdf
dc.publisher.none.fl_str_mv Taylor & Francis
publisher.none.fl_str_mv Taylor & Francis
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 13.13397

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