Tesis doctoral de Ana Belén Baltanás Bordonaba
Nadph oxidases constitute a major source of superoxide anion in hypertension. Several studies suggest an important role of nadph oxidases in different effects mediated by tgf-β1. We investigated whether a chronic treatment with p144, a peptide synthesized from type iii tgf- β1 receptor, inhibited nadph oxidases in the renal cortex of spontaneously hypertensive rats (shr). We show that chronic administration of p144 significantly reduced the nadph oxidase expression and activity as well as the nitrotyrosine levels observed in control shr rats. In addition, p144 was also able to reduce the significant increases in the renal fibrosis and in mrna expression of different components of collagen metabolism, as well as in the levels of connective tissue growth factor (ctgf) observed in shr rats. Finally, tgf-β1 stimulated nrk52e exhibited significant increases in nadph oxidase expression and activity as well as tgf-β1-dependent intracellular pathway that were inhibited in the presence of p144. for the first time, we show that p144 modulates intracellular reactive oxygen species homeostasis and regulates activation of nadph oxidases, and the subsequent renal fibrosis, by using an in vivo and in vitro system with established cell line, providing a novel therapeutic tool. We demonstrate that p144 inhibits nadph oxidases and prevents oxidative stress in kidneys from hypertensive rats. Our data also allow us to suggest that these effects may be underlying in the renal antifibrotic effect of p144.
Datos académicos de la tesis doctoral «Efectos de un péptido derivado del receptor tipo iii del tgf- β1 sobre la activación de la nadph oxidasa en el riñón de la rata espontáneamente hipertensa. consecuencias en la fibrosis renal»«
- Título de la tesis: Efectos de un péptido derivado del receptor tipo iii del tgf- β1 sobre la activación de la nadph oxidasa en el riñón de la rata espontáneamente hipertensa. consecuencias en la fibrosis renal»
- Autor: Ana Belén Baltanás Bordonaba
- Universidad: Navarra
- Fecha de lectura de la tesis: 22/06/2012
Dirección y tribunal
- Director de la tesis
- Ana Fortuño Gil
- Tribunal
- Presidente del tribunal: carmen María Vazquez cueto
- Javier Gómez ambrosi (vocal)
- david Sanz rosa (vocal)
- Ana María Briones alonso (vocal)