Publication: Análisis proteómico de exoxomas en la búsqueda de biomarcadores de nefropatía diabética
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2015-05-21
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Universidad Complutense de Madrid
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Abstract
La nefropatía diabética es la causa más común de enfermedad renal terminal. La detección temprana de riesgo de ND antes de que un daño renal avanzado haya ocurrido supondría un gran avance en la lucha contra esta enfermedad. Con ese fin, en esta tesis doctoral, se ha abordado el estudio proteómico de la ND desde dos puntos de vista distintos. Por un lado se ha llevado a cabo por primera vez un análisis cualitativo y cuantitativo del conjunto de proteínas que componen los exosomas de orina humana, en el contexto de la ND. Este estudio nos ha permitido identificar 352 proteínas cuya presencia en exosomas de orina no había sido descrita hasta el momento. Ha permitido además establecer, un panel de 25 proteínas significativamente variadas en nefropatía diabética. Por otra parte hemos estudiado el tejido renal de animales que presentaban ND en estadios tempranos. Este estudio nos ha permitido detectar cambios a nivel de expresión proteica, que ocurren al inicio de la enfermedad dando lugar a una serie de posibles biomarcadores tempranos de la misma (Regucalcina). Las técnicas desarrolladas para el aislamiento y estudio de los exosomas han sido aplicadas con éxito en las muestras de orina de estos animales que presentaban ND en estadios tempranos, pudiendo así corroborar datos obtenidos en el estudio del tejido renal.
Diabetic nephropathy (DN) is the most common cause of end-stage renal disease (ESRD). The early detection of DN before an advanced kidney injury occurs would suppose a great advance in the fight against this disease. With this aim, in this doctoral thesis, two different proteomic approaches were proposed. On the one hand a culitative and cuantitative analisys of the urine exosome proteome was preformed for the first time in ND context. This approach led us to identify 352 proteins that had not been previously described in the urine exosome proteome and allowed us to stablish a panel of 25 differentialy expressed proteins in DN. On the other hand, a proteomic analisys of kidney tissue proteins of an animal model of early of DN was performed. This study allowed us to detect significantly varied protein levels, occurring at the initial stages of the disease therefore being promising possible biomarkers for the early detecteion of DN. The techniques, here developed for the isolation and exosomal proteome analysis were successfully applied to the study of the urine exosomes of this early model of DN and permited the confirmation of the data obtained in the kidney tissue approach.
Diabetic nephropathy (DN) is the most common cause of end-stage renal disease (ESRD). The early detection of DN before an advanced kidney injury occurs would suppose a great advance in the fight against this disease. With this aim, in this doctoral thesis, two different proteomic approaches were proposed. On the one hand a culitative and cuantitative analisys of the urine exosome proteome was preformed for the first time in ND context. This approach led us to identify 352 proteins that had not been previously described in the urine exosome proteome and allowed us to stablish a panel of 25 differentialy expressed proteins in DN. On the other hand, a proteomic analisys of kidney tissue proteins of an animal model of early of DN was performed. This study allowed us to detect significantly varied protein levels, occurring at the initial stages of the disease therefore being promising possible biomarkers for the early detecteion of DN. The techniques, here developed for the isolation and exosomal proteome analysis were successfully applied to the study of the urine exosomes of this early model of DN and permited the confirmation of the data obtained in the kidney tissue approach.
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Biológicas, Departamento de Bioquímica y Biología Molecular, leída el 10-05-2013