Estudio del papel fisiopatológico de Slu7 en el hígado
- Autores: María Elizalde Arbilla
- Directores de la Tesis: Matias Antonio Ávila Zaragozá (dir. tes.), Maria del Carmen Berasain Lasarte (dir. tes.)
- Lectura: En la Universidad de Navarra ( España ) en 2014
- Idioma: español
- Tribunal Calificador de la Tesis: Juan Sastre Belloch (presid.), María Jose Iraburu Elizalde (secret.), Mª Luz Martínez Chantar (voc.), María Dolores Odero de Dios (voc.), Aranzazu Sanchez Muñoz (voc.)
- Materias:
- Enlaces
- Tesis en acceso abierto en: Dadun
- 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 4? (Hnf4?), and was critical for cAMP-regulated gene transcription. Together, out data indicate that SLU7 is central regulator of hepatocyte identity and quiescence.
