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dc.contributor.author
Atorrasagasti, Maria Catalina
dc.contributor.author
Aquino, Jorge Benjamin
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Hofman, Leonardo
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Alaniz, Laura Daniela
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Malvicini, Mariana
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Garcia, Mariana Gabriela
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Benedetti, Lorena Gabriela
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Friedman, Scott L.
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Podhajcer, Osvaldo Luis
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Mazzolini Rizzo, Guillermo Daniel
dc.date.available
2017-04-12T20:38:42Z
dc.date.issued
2011-05
dc.identifier.citation
Atorrasagasti, Maria Catalina; Aquino, Jorge Benjamin; Hofman, Leonardo; Alaniz, Laura Daniela; Malvicini, Mariana; et al.; SPARC downregulation attenuates the profibrogenic response of hepatic stellate cells induced by TGF-β1 and PDGF; American Physiological Society; American Journal Of Physiology-gastrointestinal And Liver Physiology; 300; 5; 5-2011; G739-G748
dc.identifier.uri
http://hdl.handle.net/11336/15266
dc.description.abstract
Liver fibrosis is an active process that involves changes in cell-cell and cell-extracellular matrix (ECM) interaction. Secreted protein, acidic and rich in cysteine (SPARC) is an ECM protein with many biological functions that is overexpressed in cirrhotic livers and upregulated in activated hepatic stellate cells (aHSCs). We have recently shown that SPARC downregulation ameliorates liver fibrosis in vivo. To uncover the cellular mechanisms involved, we have specifically knocked down SPARC in two aHSC lines [the CFSC-2G (rat) and the LX-2 (human)] and in primary cultured rat aHSCs. Transient downregulation of SPARC in hepatic stellate cells (HSCs) did not affect their proliferation and had only minor effects on apoptosis. However, SPARC knockdown increased HSC adhesion to fibronectin and significantly decreased their migration toward PDFG-BB and TGF-β(1). Interestingly, TGF-β(1) secretion by HSCs was reduced following SPARC small interfering RNA (siRNA) treatment, and preincubation with TGF-β(1) restored the migratory capacity of SPARC siRNA-treated cells through mechanisms partially independent from TGF-β(1)-mediated induction of SPARC expression; thus SPARC knockdown seems to exert its effects on HSCs partially through modulation of TGF-β(1) expression levels. Importantly, collagen-I mRNA expression was reduced in SPARC siRNA-transfected HSCs. Consistent with previous results, SPARC knockdown in aHSCs was associated with altered F-actin expression patterns and deregulation of key ECM and cell adhesion molecules, i.e., downregulation of N-cadherin and upregulation of E-cadherin. Our data together suggest that the upregulation of SPARC previously reported for aHSCs partially mediates profibrogenic activities of TGF-β(1) and PDGF-BB and identify SPARC as a potential therapeutic target for liver fibrosis.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
American Physiological Society
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Sparc
dc.subject
Cirrhosis
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Tgf-B
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Pdgf
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Hepatic Stellate Cells
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Otras Ciencias de la Salud
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Ciencias de la Salud
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
SPARC downregulation attenuates the profibrogenic response of hepatic stellate cells induced by TGF-β1 and PDGF
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-03-27T17:39:39Z
dc.identifier.eissn
1522-1547
dc.journal.volume
300
dc.journal.number
5
dc.journal.pagination
G739-G748
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Bethesda
dc.description.fil
Fil: Atorrasagasti, Maria Catalina. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Investigaciones Biomédicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
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Fil: Aquino, Jorge Benjamin. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Investigaciones Biomédicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
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Fil: Hofman, Leonardo. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Investigaciones Biomédicas; Argentina
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Fil: Alaniz, Laura Daniela. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Investigaciones Biomédicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
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Fil: Malvicini, Mariana. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Investigaciones Biomédicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Garcia, Mariana Gabriela. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Investigaciones Biomédicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
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Fil: Benedetti, Lorena Gabriela. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina
dc.description.fil
Fil: Friedman, Scott L.. Mount Sinai School of Medicine. Division of Liver Diseases; Estados Unidos
dc.description.fil
Fil: Podhajcer, Osvaldo Luis. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina
dc.description.fil
Fil: Mazzolini Rizzo, Guillermo Daniel. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Investigaciones Biomédicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.journal.title
American Journal Of Physiology-gastrointestinal And Liver Physiology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://ajpgi.physiology.org/content/300/5/G739.long
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1152/ajpgi.00316.2010


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