(Institución)/></a>
				</td>
				<td class= (Institución)
   (Nuevo usuario)
Ayuda  | Contacto  |  Castellano English  
 

Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Terapia génica y Hepatología > Genética molecular > DA - CIMA - Terapia génica y Hepatología - Genética molecular - Artículos de Revista >

Oral methylthioadenosine administration attenuates fibrosis and chronic liver disease progression in Mdr2-/- mice
Autor(es) : Latasa, M.U. (María Ujué)
Gil-Puig, C. (Carmen)
Fernandez-Barrena, M.G. (Maite G.)
Rodriguez-Ortigosa, C.M. (Carlos M.)
Banales, J.M. (Jesús M.)
Urtasun, R. (Raquel)
Goñi, S. (Saioa)
Mendez, M. (Miriam)
Arcelus, S. (Sara)
Juanarena, N. (Nerea)
Recio, J.A. (Juan A.)
Lotersztajn, S. (Sophie)
Prieto, J. (Jesús)
Berasain, C. (Carmen)
Corrales, F.J. (Fernando José)
Lecanda, J. (Jon)
Avila, M.A. (Matías Antonio)
Palabras clave : Adenosine/analogs & derivatives
Fibrosis/drug therapy
Liver Diseases/genetics
Liver Diseases/pathology
P-Glycoproteins/genetics
Thionucleosides/administration & dosage
Fecha incorporación: 2010
Editorial : Public Library of Science
Versión del editor: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0015690
ISSN: 1932-6203
Cita: Latasa MU, Gil-Puig C, Fernandez-Barrena MG, Rodriguez-Ortigosa CM, Banales JM, Urtasun R, et al. Oral methylthioadenosine administration attenuates fibrosis and chronic liver disease progression in Mdr2-/- mice. PLoS One 2010 Dec 29;5(12):e15690.
Resumen
BACKGROUND: Inflammation and fibrogenesis are directly related to chronic liver disease progression, including hepatocellular carcinoma (HCC) development. Currently there are few therapeutic options available to inhibit liver fibrosis. We have evaluated the hepatoprotective and anti-fibrotic potential of orally-administered 5'-methylthioadenosine (MTA) in Mdr2(-/-) mice, a clinically relevant model of sclerosing cholangitis and spontaneous biliary fibrosis, followed at later stages by HCC development. METHODOLOGY: MTA was administered daily by gavage to wild type and Mdr2(-/-) mice for three weeks. MTA anti-inflammatory and anti-fibrotic effects and potential mechanisms of action were examined in the liver of Mdr2(-/-) mice with ongoing fibrogenesis and in cultured liver fibrogenic cells (myofibroblasts). PRINCIPAL FINDINGS: MTA treatment reduced hepatomegaly and liver injury. α-Smooth muscle actin immunoreactivity and collagen deposition were also significantly decreased. Inflammatory infiltrate, the expression of the cytokines IL6 and Mcp-1, pro-fibrogenic factors like TGFβ2 and tenascin-C, as well as pro-fibrogenic intracellular signalling pathways were reduced by MTA in vivo. MTA inhibited the activation and proliferation of isolated myofibroblasts and down-regulated cyclin D1 gene expression at the transcriptional level. The expression of JunD, a key transcription factor in liver fibrogenesis, was also reduced by MTA in activated myofibroblasts. CONCLUSIONS/SIGNIFICANCE: Oral MTA administration was well tolerated and proved its efficacy in reducing liver inflammation and fibrosis. MTA may have multiple molecular and cellular targets. These include the inhibition of inflammatory and pro-fibrogenic cytokines, as well as the attenuation of myofibroblast activation and proliferation. Downregulation of JunD and cyclin D1 expression in myofibroblasts may be important regarding the mechanism of action of MTA. This compound could be a good candidate to be tested for the treatment of (biliary) liver fibrosis.
Enlace permanente: http://hdl.handle.net/10171/20237
Aparece en las colecciones: DA - CIMA - Servicios de apoyo - Instalación radioactiva - Artículos
DA - CIMA - Terapia génica y Hepatología - Oncobiología - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Hepatología experimental - Artículos de revista
DA - CIMA - Unidad de Proteómica, Genómica y Bioinformática - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Hepatología bioquímica - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Genética molecular - Artículos de Revista

Ficheros en este registro:
Fichero:  journal.pone.0015690.pdf
Descripción: 
Tamaño:  3,76 MB
Formato:  Adobe PDF
 Visualizar / Abrir 

Los ítems de Dadun están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.