Publication: Estudio del papel del péptido antagonista de TGF-B1, P17, en el desarrollo de estenosis traqueal en un modelo animal
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2021-07-07
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Universidad Complutense de Madrid
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Abstract
La estenosis traqueal adquirida benigna de origen inflamatorio es un problema con gran impacto sobre la calidad de vida para el paciente adulto y pediátrico, en ocasiones con necesidad de traqueostomía permanente o tratamientos recurrentes de por vida. Aunque en la actualidad existen diversas opciones terapéuticas todas ellas presentan limitaciones y por el momento no se han desarrollado tratamientos basados en su fundamento fisiopatológico. Es conocido el papel relevante de diversos agentes moleculares implicados en los procesos de fibrosis y cicatrización siendo el TGF-β uno demás importantes y también la activación de la vía intracelular JAK/STAT. Los objetivos fundamentales de esta tesis son comprobar el papel de TGF-β y la activación de la vía JAK/STAT en la fisiopatología de la estenosis traqueal inflamatoria humana y en animal de experimentación, mediante la obtención y validación de un modelo experimental estenosis traqueal con el fin de evaluar el potencial antifibrótico de la aplicación local del péptido P17, como antagonista de TGF-β 1 y de Baricitinib, como inhibidor de la vía JAK/STAT..
Benign acquired inflammatory tracheal stenosis is aproblem with great impact on quality of life for the adult and pediatric patient, sometimes in need of permanent tracheostomy or recurrent lifelong treatments. Although there are currently various therapeutic options, all of them have limitations and, at the moment, no treatments have been developed based on their pathophysiological basis. The relevant role of various molecular agents involved in fibrosis and healing processes is well known, with TGF-β being one of the most important and also the activation of the intracellular JAK/STATpathway. The main objectives of this thesis are to verify the role of TGF-β and the activation of the JAK/STAT pathway in the pathophysiology of human inflammatory tracheal stenosis and in experimental animals, by obtaining and validating an experimental model of tracheal stenosis in order to evaluate the antifibrotic potential of the local application of the P17 peptide, as an antagonist of TGF-β 1 and Baricitinib, as an inhibitor of the JAK/STAT pathway...
Benign acquired inflammatory tracheal stenosis is aproblem with great impact on quality of life for the adult and pediatric patient, sometimes in need of permanent tracheostomy or recurrent lifelong treatments. Although there are currently various therapeutic options, all of them have limitations and, at the moment, no treatments have been developed based on their pathophysiological basis. The relevant role of various molecular agents involved in fibrosis and healing processes is well known, with TGF-β being one of the most important and also the activation of the intracellular JAK/STATpathway. The main objectives of this thesis are to verify the role of TGF-β and the activation of the JAK/STAT pathway in the pathophysiology of human inflammatory tracheal stenosis and in experimental animals, by obtaining and validating an experimental model of tracheal stenosis in order to evaluate the antifibrotic potential of the local application of the P17 peptide, as an antagonist of TGF-β 1 and Baricitinib, as an inhibitor of the JAK/STAT pathway...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, Departamento de Cirugía, leída el 01/02/2021