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The Global ETD Search service is a free service for researchers
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Networked Digital Library of Theses and Dissertations.
Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
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Showing 41 to 45 of 45 (0.016 seconds)Spelling suggestions: "subject:"smad3"" "subject:"mad3""
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The Role of MMPs, Smad3 and Heat Shock Proteins in TGF-β-Induced Anterior Subcapsular Cataract DevelopmentBanh, Alice January 2007 (has links)
Transforming growth factor beta (TGF-β) has been implicated in anterior subcapsular cataract (ASC) development. In the first section of this thesis, an in-vitro rat lens model was used to determine the role of matrix metalloproteinases during TGF-β-induced ASC. In the second part, an in-vivo TGF-β transgenic and Smad3 knockout model was used to examine the role of Smad3 signaling pathway in TGF-β-induced ASC development. Lastly, an in-vitro rat lens epithelial explant culture model was used to investigate the potential role of heat shock proteins (Hsps) in TGF-β-induced epithelial-mesenchymal transition (EMT). Optical, morphological and molecular changes were analyzed in theses studies.
Results from cultured rat lenses show a significant increase of back vertex distance variability (decrease of sharpness and focus) during ASC development. Inhibition of MMPs eliminated the TGF-β-induced plaque formation. Similarly, the overexpression of TGF-β1 in transgenic mouse lenses leads to ASC formation and a decrease in lens optical quality in comparison to wild-type lenses, while TGF-β1/Smad3-/- (null) lenses show diminished TGF-β-induced effects. The plaques formed in the TGF-β1/Smad3-/- lenses are substantially smaller than in the TGF-β1/Smad3+/+ lenses. The morphological and molecular changes of TGF-β2/FGF-2 treated rat lens epithelial explants are similar to those found in the TGF-β2 treated rat lenses and transgenic TGF-β1 mouse lenses. Heat shock treatment prior to TGF-β treatment significantly reduced the effects of EMT in rat LECs.
In conclusion, MMP inhibition prevented TGF-β-induced ASC formation whereas heat shock treatment and the absence of Smad3 protein expression only reduced the severity of TGF-β-induced effects.
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Investigating TGFβ signals in cell fate specification in the early mouse embryoSenft, Anna Dorothea January 2016 (has links)
TGFβ signalling via Smad transcription factors is essential for axis patterning and subsequent cell fate specification during mammalian embryogenesis. However, the cellular and molecular mechanisms have been difficult to characterise in vivo due to early embryonic lethality of mouse mutants and redundant functional activities. Here I show that combined deletion of closely related Smad2 and Smad3 in mouse embryonic stem cells impairs induction of lineage specific gene expression during differentiation, while extra-embryonic gene expression is up-regulated. Preliminary data suggest that the underlying mechanism of this differentiation defect reflects the inability of Smad2/3<sup>-/-</sup> cells to establish lineage priming. Collectively, these findings identify novel downstream target genes controlled by Smad2/3 and an absolute requirement for Smad2/3 during embryonic differentiation. TGFβ signalling via Smad1 and Smad4 is essential for induction of the transcription factor Blimp1 required for primordial germ cell specification. The direct upstream regulators of Blimp1 are unknown, but T-box factors have recently been suggested to play a role. In a second project, I performed tissue- specific ablation of the T-box transcription factor Eomes as well as components of the TGFβ signalling pathway in either the visceral endoderm or the epiblast to examine tissue-specific functions for Blimp1 induction. I show that Eomes and Smad2 functions in the visceral endoderm as well as Eomes function in the epiblast are dispensable for Blimp1 induction, but rather are required to restrict Blimp1 induction to posterior epiblast cells. In contrast, epiblast-specific Smad4 or Smad1 mutants fail to robustly induce Blimp1 in the epiblast. My preliminary analysis suggests that competence to induce primordial germ cell fate is dependent on the interplay of Smad2/Eomes functions in the visceral endoderm and Smad1/4 functions in the epiblast. Collectively, this thesis provides insight into the transition from pluripotency to cell fate specification in the mammalian embryo that is impossible to obtain from human embryos in vivo.
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Dynamic interplay between activators and repressors of smooth muscle alpha-actin gene transcription during myofibroblast differentiationHariharan, Seethalakshmi 19 August 2014 (has links)
No description available.
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The Paradoxical Roles of Oncostatin M in Mammary Epithelial Cell Senescence and TransformationBryson, Benjamin Levi 02 February 2018 (has links)
No description available.
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Role of Ring1B in ephitelial to mesenchimal transition, invasion and migration of mammary epithelial cellsBosch Gutiérrez, Almudena 21 December 2009 (has links)
The Polycomb group (PcG) family of proteins form chromatin-modifying complexes essential for embryonic development, and stem cell renewal and are commonly deregulated in cancer. There are several reports that address the possible implication of PcG proteins in tumor progression and metastasis, but very little is known about the specific role of these proteins in tumor progression and invasion. On the other hand, the molecular processes of the worst cancer prognosis, metastasis, which leads to an incurable disease, are yet incompletely elucidated. Here we show a role for Ring1B, a PcG protein, in three processes related to metastasis: in the Epithelial-mesenchymal transition (EMT), a critical morphogenic event that occurs during embryonic development and during the progression of various epithelial tumors, an in the migration and the invasion of mammary epithelial cells. / Las proteínas del grupo Polycomb (PcG) forman complejos modificadores de la cromatina esenciales en el desarrollo embrionario y en la renovación de las células madre, y su desregulación ha sido asociada al cáncer. Varios estudios muestran la posible implicación de las proteínas de PcG en la progresión tumoral y en la metástasis, pero a pesar de ello se sabe muy poco de los procesos moleculares en los que estas proteínas están participando. Por otro lado, los procesos moleculares responsables del peor pronóstico en cáncer, la metástasis, que continua siendo una enfermedad incurable, siguen sin estar completamente elucidados. En esta disertación mostramos el papel de Ring1B, una proteína del PcG, en tres procesos implicados en la metástasis: en la transición epitelio-mesénquima (EMT), un proceso morfogénico crítico en el desarrollo embrionario y durante la progresión de varios cánceres epiteliales, y en la migración y la invasión de las células epiteliales mamarias.
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