Browsing by Subject "TGFβ"

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    Implicación de SIRT1, una desacetilasa dependiente de NAD+, en la regulación de la transcripción por TGFβ.
    (2013-06-24) García Vizcaíno, Eva María; Nicolás Villaescusa, Francisco José; Departamentos y Servicios::Departamentos de la UMU::Genética y Microbiología
    RESUMEN (150 PALABRAS): TGFβ produce numerosas respuestas en células eucarióticas. Los principales mediadores de la señalización de TGFβ son las Smad. Proteínas accesorias que interaccionen con las Smads pueden ser responsables de parte de las respuestas de TGFβ. En una búsqueda de nuevas proteínas que interaccionan con Smad2, utilizando el Sistema Doble Híbrido Cyto-Trap, hemos hallado 110 proteínas diferentes. Entre ellas, encontramos Sirt1, una desacetilasa de histonas de tipo III dependiente de NAD+. Hemos realizado un estudio del papel del Sirt1 en la señalización de TGFβ. Hemos mostrado la interacción Smad2/Sirt1 in vivo e in vitro. Hemos realizado un amplio estudio molecular y funcional de la interacción Smad2/Sirt1. Determinamos que Sirt1 no desacetila a Smad2, pero está involucrada en la regulación dependiente de TGFβ de cierto grupo de genes. Finalmente, asociamos el papel de Sirt1 en la regulación de la transcripción por TGFβ a genes específicos que quedan agrupados en funciones celulares concretas. PALABRAS CLAVE: TGFβ, SMAD2, SIRT1, DESACETILASA DE HISTONAS, ACETILACIÓN, DESACETILACIÓN, REGULACIÓN DE LA TRANSCRIPCIÓN, CÁNCER. THESIS TITLE: IMPLICATION OF SIRT1, A NAD+ DEPENDENT DEACETYLASE, IN TGFβ TRANSCRIPTION REGULATION. ABSTRACT (150 WORDS): TGFβ is able to generate a numerous responses in eukaryotic cells. The main mediators in TGFβ signalling are the Smad proteins. Accessory Smad interacting proteins could be responsible for a fraction of the TGFβ-dependent responses. In a search for new Smad2 interacting proteins by using the Cyto Trap Two Hybrid System, we have found 110 different proteins. Among them, we found Sirt1, a type III histone deacetylase dependent on NAD+. We have studied the role of Sirt1 in TGFβ signalling. We have showed that Smad2 and Sirt1 interact both in vivo and in vitro. We did a deep molecular and functional study of the Smad2/Sirt1 interaction. We have shown that Sirt1 does not deacetylase Smad2 but it is involved in TGFβ-dependent transcription of certain set of genes. Finally, we have linked Sirt1 role to TGFβ dependent regulation of genes associated to specific cell processes. KEYWORDS: TGFβ, SMAD2, SIRT1, HISTONE DEACETYLASE, ACETYLATION, DESACETYLATION, TRANSCRIPTION REGULATION, CANCER.
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    Temporal and spatial distribution of TGF-B isoforms and signaling intermediates in corneal regenerative wound repair
    (Murcia : F. Hernández, 2009) Huh, Man-IL; Chang, Yongmin; Jung, Jae-Chang
    The present study analyzed the temporal and spatial expression of TGF-ß isoforms and activated pSmad2 and p38MAPK during epithelial debridement wound repair, using chick cornea by immunohistochemistry. Normal corneas showed low-level TGFßs staining. Following wounding, TGF-ß1 expression was strong in the Bowman’s layer (BL). TGF-ß3 expression was confined to basal cells in the regenerating and unwounded regions, and was not detected in migrating epithelial, stromal or endothelial cells. In addition, TGF-ß3 treatment stimulated the proliferation of cultured epithelial cells. Our present findings seem to suggest that the TGF-ß3 signal may be required for epithelial cell proliferation. TGF-ß2 expression was strong in migrating and proliferating epithelial cells, many active migrating fibroblasts at the wound edge, endothelial cells and Descemet’s membrane (DM). Although both nuclear pSmad2 and p38MAPK staining was observed in many basal epithelial cells, pSmad2 positive cells were co-localized with PCNA positive cells. Therefore, it seems likely that the pSmad2 signal may affect epithelial cell proliferation in healing corneas. Both pSmad2 and p38MAPK expression were also observed in endothelial cells. Interestingly, many active fibroblasts over the whole stroma in early wound healing at day 2 expressed nuclear pSmad2, but little if any cytoplasmic p38MAPK. Collectively, temporal/spatial up-regulation and distribution of the three TGF-ß isoforms, as well as concerted activation of both Smad2 and p38MAPK, appears to be a key aspect of regenerative corneal wound healing in the chick.