Estudio del papel fisiopatológico de Slu7 en el hígado
Palabras clave : 
Procesos metabólicos
Bioquímica molecular
Metabolismo humano
Oncología clínica
Materias Investigacion::Ciencias de la vida
Fecha de publicación: 
2014
Fecha de la defensa: 
24-jun-2014
Editorial : 
Servicio de Publicaciones de la Universidad de Navarra
Cita: 
ELIZALDE, M. “Estudio del papel fisiopatológico de Slu7 en el hígado”. Berasain, C. y Avila, M. (dirs). Tesis doctoral. Universidad de Navarra, Pamplona, 2014
Resumen
A precise equilibrium between cellular differentiation and proliferation is fundamental for tissue homeostasis. Maintaining this balance is particularly important for the liver, a highly differentiated organ with systemic metabolic functions that is endowed with unparalleled regenerative potential. Carcinogenesis in the liver develops as the result of hepatocellular de-differentiation and uncontrolled proliferation. Here, we identified SLU7, which encodes a pre-mRNA splicing regulator that is inhibited in hepatocarcinoma, as a pivotal gene for hepatocellular homeostasis. SLU7 knockdown in human liver cells and mouse liver resulted in profound changes in pre-mRNA splicing and gene expression, leading to impaired glucose and lipid metabolism, refractoriness to key metabolic hormones, and reversion to a fetal-like gene expression pattern. Additionally, loss of SLU7 also increased hepatocellular proliferation and induced a switch to a tumor-like glycolytic phenotype. Slu7 governed the splicing and/or expression of multiple genes essential for hepatocellular differentiation, including serine/arginine-rich splicing factor 3 (Srsf3) and hepatocyte nuclear factor 4α (Hnf4α), and was critical for cAMP-regulated gene transcription. Together, out data indicate that SLU7 is central regulator of hepatocyte identity and quiescence.

Ficheros en este registro:
Fichero: 
Tesis_MariaElizaldeArbilla.pdf
Descripción: 
Tamaño: 
7,24 MB
Formato: 
Adobe PDF


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