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....
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| Format: | info:eu-repo/semantics/doctoralThesis |
| Language: | spa |
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Servicio de Publicaciones de la Universidad de Navarra
2014
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10171/37155 |
| _version_ | 1793400566595977216 |
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| author | Elizalde, M. (María) Berasain, C. (Carmen) Avila, M.A. (Matías Antonio) |
| author_facet | Elizalde, M. (María) Berasain, C. (Carmen) Avila, M.A. (Matías Antonio) |
| author_sort | Elizalde, M. (María) |
| collection | DSpace |
| description | 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. |
| format | info:eu-repo/semantics/doctoralThesis |
| id | oai:dadun.unav.edu:10171-37155 |
| institution | Universidad de Navarra |
| language | spa |
| publishDate | 2014 |
| publisher | Servicio de Publicaciones de la Universidad de Navarra |
| record_format | dspace |
| spelling | oai:dadun.unav.edu:10171-371552020-03-03T11:23:15Z Estudio del papel fisiopatológico de Slu7 en el hígado Elizalde, M. (María) Berasain, C. (Carmen) Avila, M.A. (Matías Antonio) Procesos metabólicos Bioquímica molecular Metabolismo humano Oncología clínica Materias Investigacion::Ciencias de la vida 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. 2014-12-09T17:03:39Z 2014-12-09T17:03:39Z 2014 2014-06-24 info:eu-repo/semantics/doctoralThesis https://hdl.handle.net/10171/37155 spa info:eu-repo/semantics/openAccess application/pdf Servicio de Publicaciones de la Universidad de Navarra |
| spellingShingle | Procesos metabólicos Bioquímica molecular Metabolismo humano Oncología clínica Materias Investigacion::Ciencias de la vida Elizalde, M. (María) Berasain, C. (Carmen) Avila, M.A. (Matías Antonio) Estudio del papel fisiopatológico de Slu7 en el hígado |
| title | Estudio del papel fisiopatológico de Slu7 en el hígado |
| title_full | Estudio del papel fisiopatológico de Slu7 en el hígado |
| title_fullStr | Estudio del papel fisiopatológico de Slu7 en el hígado |
| title_full_unstemmed | Estudio del papel fisiopatológico de Slu7 en el hígado |
| title_short | Estudio del papel fisiopatológico de Slu7 en el hígado |
| title_sort | estudio del papel fisiopatológico de slu7 en el hígado |
| topic | Procesos metabólicos Bioquímica molecular Metabolismo humano Oncología clínica Materias Investigacion::Ciencias de la vida |
| url | https://hdl.handle.net/10171/37155 |
| work_keys_str_mv | AT elizaldemmaria estudiodelpapelfisiopatologicodeslu7enelhigado AT berasainccarmen estudiodelpapelfisiopatologicodeslu7enelhigado AT avilamamatiasantonio estudiodelpapelfisiopatologicodeslu7enelhigado |