Estudio del papel fisiopatológico de Slu7 en el hígado
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....
| Autor: | |
|---|---|
| Tipo de documento: | tese |
| Data de publicação: | 2014 |
| País: | España |
| Recursos: | Universidad de Navarra |
| Repositório: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Idioma: | espanhol |
| OAI Identifier: | oai:dadun.unav.edu:10171/37155 |
| Acesso em linha: | https://hdl.handle.net/10171/37155 |
| Access Level: | Acceso aberto |
| Palavra-chave: | Procesos metabólicos Bioquímica molecular Metabolismo humano Oncología clínica Materias Investigacion::Ciencias de la vida |
| Resumo: | 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. |
|---|